Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing
Abstract
:1. Introduction
2. Disadvantages of scFv-Based CARs in Comparison to Natural Receptor-/Ligand-Based CAR T Cells
2.1. scFv Instability and Domain Swapping Leads to scFv Aggregation and Tonic CAR Signaling
2.2. scFv Immunogenicity
2.3. Antigen Escape
2.4. Target Recognition through Evolved Ligand Affinity vs. Antibody Directed scFv Affinity
2.5. Ease of Preclinical Development Plans
3. Challenges of Natural Receptor- and Ligand-Based CARs
3.1. Off-Tumor Toxicity
3.2. Competition with Endogenous Ligands
3.3. Unintentional Signaling through Targeted Receptor
4. Natural Receptor- and Ligand-Based CAR T Cell Therapies in Preclinical Studies
4.1. B7H6
4.2. EGFR
4.3. FLT3
4.4. IL-10R
4.5. MPL
4.6. IL-11Rα
4.7. PVR/Nectin-2
4.8. EPHB4
5. Natural Receptor- and Ligand-Based CAR T Cell Therapies in Early Phase Clinical Testing
5.1. NKG2D Ligands
5.2. IL-13Rα2
5.3. ErbB Family
5.4. BCMA/TACI
5.5. MMP2+ GBM
5.6. ICAM-1
5.7. FSHR
5.8. CD70
5.9. GMR
5.10. Antibody-Coupled T-cell Receptor (ACTR)
6. Summary
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Kuwana, Y.; Asakura, Y.; Utsunomiya, N.; Nakanishi, M.; Arata, Y.; Itoh, S.; Nagase, F.; Kurosawa, Y. Expression of chimeric receptor composed of immunoglobulin-derived V resions and T-cell receptor-derived C regions. Biochem. Biophys. Res. Commun. 1987, 149, 960–968. [Google Scholar] [CrossRef]
- Gross, G.; Waks, T.; Eshhar, Z. Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc. Natl. Acad. Sci. USA 1989, 86, 10024–10028. [Google Scholar] [CrossRef] [Green Version]
- Eshhar, Z.; Waks, T.; Gross, G.; Schindler, D.G. Specific activation and targeting of cytotoxic lymphocytes through chimeric single chains consisting of antibody-binding domains and the gamma or zeta subunits of the immunoglobulin and T-cell receptors. Proc. Natl. Acad. Sci. USA 1993, 90, 720–724. [Google Scholar] [CrossRef] [Green Version]
- Brocker, T.; Peter, A.; Traunecker, A.; Karjalainen, K. New simplified molecular design for functional T cell receptor. Eur. J. Immunol. 1993, 23, 1435–1439. [Google Scholar] [CrossRef] [Green Version]
- Maude, S.L.; Frey, N.; Shaw, P.A.; Aplenc, R.; Barrett, D.M.; Bunin, N.J.; Chew, A.; Gonzalez, V.E.; Zheng, Z.; Lacey, S.F. Chimeric antigen receptor T cells for sustained remissions in leukemia. N. Engl. J. Med. 2014, 371, 1507–1517. [Google Scholar] [CrossRef] [Green Version]
- Davila, M.L.; Riviere, I.; Wang, X.; Bartido, S.; Park, J.; Curran, K.; Chung, S.S.; Stefanski, J.; Borquez-Ojeda, O.; Olszewska, M. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 2014, 6, ra224–ra225. [Google Scholar] [CrossRef] [Green Version]
- Turtle, C.J.; Hanafi, L.A.; Berger, C.; Gooley, T.A.; Cherian, S.; Hudecek, M.; Sommermeyer, D.; Melville, K.; Pender, B.; Budiarto, T.M.; et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J. Clin. Investig. 2016, 126, 2123–2138. [Google Scholar] [CrossRef] [Green Version]
- Abramson, J.S.; Palomba, M.L.; Gordon, L.I.; Lunning, M.A.; Wang, M.; Arnason, J.; Mehta, A.; Purev, E.; Maloney, D.G.; Andreadis, C.; et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet 2020, 396, 839–852. [Google Scholar] [CrossRef]
- Munshi, N.C.; Anderson, L.D.; Shah, N.; Madduri, D.; Berdeja, J.; Lonial, S.; Raje, N.; Lin, Y.; Siegel, D.; Oriol, A.; et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N. Engl. J. Med. 2021, 384, 705–716. [Google Scholar] [CrossRef]
- Wang, M.; Munoz, J.; Goy, A.; Locke, F.L.; Jacobson, C.A.; Hill, B.T.; Timmerman, J.M.; Holmes, H.; Jaglowski, S.; Flinn, I.W.; et al. KTE-X19 CAR T Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma. N. Engl. J. Med. 2020, 382, 1331–1342. [Google Scholar] [CrossRef]
- Gill, S.; Maus, M.V.; Porter, D.L. Chimeric antigen receptor T cell therapy: 25years in the making. Blood Rev. 2016, 30, 157–167. [Google Scholar] [CrossRef]
- Rafiq, S.; Hackett, C.S.; Brentjens, R.J. Engineering strategies to overcome the current roadblocks in CAR T cell therapy. Nat. Rev. Clin. Oncol. 2020, 17, 147–167. [Google Scholar] [CrossRef]
- Guest, R.D.; Hawkins, R.E.; Kirillova, N.; Cheadle, E.J.; Arnold, J.; O’Neill, A.; Irlam, J.; Chester, K.A.; Kemshead, J.T.; Shaw, D.M. The role of extracellular spacer regions in the optimal design of chimeric immune receptors: Evaluation of four different scFvs and antigens. J. Immunother. 2005, 28, 203–211. [Google Scholar] [CrossRef]
- Watanabe, N.; Bajgain, P.; Sukumaran, S.; Ansari, S.; Heslop, H.E.; Rooney, C.M.; Brenner, M.K.; Leen, A.M.; Vera, J.F. Fine-tuning the CAR spacer improves T-cell potency. Oncoimmunology 2016, 5, e1253656. [Google Scholar] [CrossRef] [Green Version]
- Hudecek, M.; Sommermeyer, D.; Kosasih, P.L.; Silva-Benedict, A.; Liu, L.; Rader, C.; Jensen, M.C.; Riddell, S.R. The Nonsignaling Extracellular Spacer Domain of Chimeric Antigen Receptors Is Decisive for In Vivo Antitumor Activity. Cancer Immunol. Res. 2015, 3, 125–135. [Google Scholar] [CrossRef] [Green Version]
- James, S.E.; Greenberg, P.D.; Jensen, M.C.; Lin, Y.; Wang, J.; Till, B.G.; Raubitschek, A.A.; Forman, S.J.; Press, O.W. Antigen Sensitivity of CD22-Specific Chimeric TCR Is Modulated by Target Epitope Distance from the Cell Membrane. J. Immunol. 2008, 180, 7028–7038. [Google Scholar] [CrossRef] [Green Version]
- Wang, W.; Singh, S.; Zeng, D.L.; King, K.; Nema, S. Antibody Structure, Instability, and Formulation. J. Pharm. Sci. 2007, 96, 1–26. [Google Scholar] [CrossRef]
- Nieba, L.; Honegger, A.; Krebber, C.; Pluckthun, A. Disrupting the hydrophobic patches at the antibody variable/constant domain interface: Improved in vivo folding and physical characterization of an engineered scFv fragment. Protein Eng. Des. Sel. 1997, 10, 435–444. [Google Scholar] [CrossRef]
- Arndt, K.M.; Müller, K.M.; Plückthun, A. Factors Influencing the Dimer to Monomer Transition of an Antibody Single-Chain Fv Fragment. Biochemistry 1998, 37, 12918–12926. [Google Scholar] [CrossRef]
- Bennett, M.J.; Choe, S.; Eisenberg, D. Domain swapping: Entangling alliances between proteins. Proc. Natl. Acad. Sci. USA 1994, 91, 3127–3131. [Google Scholar] [CrossRef] [Green Version]
- Bennett, M.J.; Schlunegger, M.P.; Eisenberg, D. 3D domain swapping: A mechanism for oligomer assembly. Protein Sci. 1995, 4, 2455–2468. [Google Scholar] [CrossRef] [Green Version]
- Lamers, C.H.J.; Willemsen, R.; Van Elzakker, P.; Van Steenbergen-Langeveld, S.; Broertjes, M.; Oosterwijk-Wakka, J.; Oosterwijk, E.; Sleijfer, S.; Debets, R.; Gratama, J.W. Immune responses to transgene and retroviral vector in patients treated with ex vivo–engineered T cells. Blood 2011, 117, 72–82. [Google Scholar] [CrossRef] [Green Version]
- Long, A.H.; Haso, W.M.; Shern, J.F.; Wanhainen, K.M.; Murgai, M.; Ingaramo, M.; Smith, J.P.; Walker, A.J.; Kohler, M.E.; Venkateshwara, V.R.; et al. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat. Med. 2015, 21, 581–590. [Google Scholar] [CrossRef] [Green Version]
- Frigault, M.J.; Lee, J.; Basil, M.C.; Carpenito, C.; Motohashi, S.; Scholler, J.; Kawalekar, O.U.; Guedan, S.; McGettigan, S.E.; Posey, A.D.; et al. Identification of Chimeric Antigen Receptors That Mediate Constitutive or Inducible Proliferation of T Cells. Cancer Immunol. Res. 2015, 3, 356–367. [Google Scholar] [CrossRef] [Green Version]
- Gil, D.; Schrum, A.G. Strategies to stabilize compact folding and minimize aggregation of antibody-based fragments. Adv. Biosci. Biotechnol. 2013, 4, 73–84. [Google Scholar] [CrossRef] [Green Version]
- Todorovska, A.; Roovers, R.C.; Dolezal, O.; Kortt, A.A.; Hoogenboom, H.R.; Hudson, P.J. Design and application of diabodies, triabodies and tetrabodies for cancer targeting. J. Immunol. Methods 2001, 248, 47–66. [Google Scholar] [CrossRef]
- Dolezal, O.; De Gori, R.; Walter, M.; Doughty, L.; Hattarki, M.; Hudson, P.J.; Kortt, A.A. Single-chain Fv multimers of the anti-neuraminidase antibody NC10: The residue at position 15 in the VL domain of the scFv-0 (VL−VH) molecule is primarily responsible for formation of a tetramer–trimer equilibrium. Protein Eng. Des. Sel. 2003, 16, 47–56. [Google Scholar] [CrossRef] [Green Version]
- Whitlow, M.; Filpula, D.; Rollence, M.L.; Feng, S.-L.; Wood, J.F. Multivalent Fvs: Characterization of single-chain Fv oligomers and preparation of a bispecific Fv. Protein Eng. Des. Sel. 1994, 7, 1017–1026. [Google Scholar] [CrossRef] [PubMed]
- Wu, A.M.; Tan, G.J.; Sherman, M.A.; Clarke, P.; Olafsen, T.; Forman, S.J.; Raubitschek, A.A. Multimerization of a chimeric anti-CD20 single-chain Fv-Fc fusion protein is mediated through variable domain exchange. Protein Eng. Des. Sel. 2001, 14, 1025–1033. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Salzer, B.; Schueller, C.M.; Zajc, C.U.; Peters, T.; Schoeber, M.A.; Kovacic, B.; Buri, M.C.; Lobner, E.; Dushek, O.; Huppa, J.B.; et al. Engineering AvidCARs for combinatorial antigen recognition and reversible control of CAR function. Nat. Commun. 2020, 11, 4166. [Google Scholar] [CrossRef] [PubMed]
- Holliger, P.; Prospero, T.; Winter, G. “Diabodies”: Small bivalent and bispecific antibody fragments. Proc. Natl. Acad. Sci. USA 1993, 90, 6444–6448. [Google Scholar] [CrossRef] [Green Version]
- Pack, P.; Kujau, M.; Schroeckh, V.; Knüpfer, U.; Wenderoth, R.; Riesenberg, D.; Plückthun, A. Improved Bivalent Miniantibodies, with Identical Avidity as Whole Antibodies, Produced by High Cell Density Fermentation of Escherichia coli. Nat. Biotechnol. 1993, 11, 1271–1277. [Google Scholar] [CrossRef]
- Pack, P.; Plueckthun, A. Miniantibodies: Use of amphipathic helixes to produce functional, flexibly linked dimeric FV fragments with high avidity in Escherichia coli. Biochemistry 1992, 31, 1579–1584. [Google Scholar] [CrossRef]
- Braun, A.; Kwee, L.; Labow, M.A.; Alsenz, J. Protein aggregates seem to play a key role among the parameters influencing the antigenicity of interferon alpha (IFN-alpha) in normal and transgenic mice. Pharm. Res. 1997, 14, 1472–1478. [Google Scholar] [CrossRef] [PubMed]
- Hermeling, S.; Crommelin, D.J.A.; Schellekens, H.; Jiskoot, W. Structure-Immunogenicity Relationships of Therapeutic Proteins. Pharm. Res. 2004, 21, 897–903. [Google Scholar] [CrossRef] [PubMed]
- Van Oers, N.; Tao, W.; Watts, J.D.; Johnson, P.; Aebersold, R.; Teh, H.S. Constitutive tyrosine phosphorylation of the T-cell receptor (TCR) zeta subunit: Regulation of TCR-associated protein tyrosine kinase activity by TCR zeta. Mol. Cell. Biol. 1993, 13, 5771–5780. [Google Scholar] [PubMed] [Green Version]
- Van Oers, N.S.; Killeen, N.; Welss, A. ZAP-70 is constitutively associated with tyrosine-phosphorylated TCR ζ in murine thymocytes and lymph node T cells. Immunity 1994, 1, 675–685. [Google Scholar] [CrossRef]
- Ajina, A.; Maher, J. Strategies to Address Chimeric Antigen Receptor Tonic Signaling. Mol. Cancer 2018, 17, 1795–1815. [Google Scholar] [CrossRef] [Green Version]
- Myers, D.R.; Zikherman, J.; Roose, J.P. Tonic Signals: Why Do Lymphocytes Bother? Trends Immunol. 2017, 38, 844–857. [Google Scholar] [CrossRef] [PubMed]
- Hochweller, K.; Wabnitz, G.H.; Samstag, Y.; Suffner, J.; Hammerling, G.J.; Garbi, N. Dendritic cells control T cell tonic signaling required for responsiveness to foreign antigen. Proc. Natl. Acad. Sci. USA 2010, 107, 5931–5936. [Google Scholar] [CrossRef] [Green Version]
- Eyquem, J.; Mansilla-Soto, J.; Giavridis, T.; van der Stegen, S.J.; Hamieh, M.; Cunanan, K.M.; Odak, A.; Gönen, M.; Sadelain, M. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature 2017, 543, 113–117. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gomes-Silva, D.; Mukherjee, M.; Srinivasan, M.; Krenciute, G.; Dakhova, O.; Zheng, Y.; Cabral, J.M.S.; Rooney, C.M.; Orange, J.S.; Brenner, M.K.; et al. Tonic 4-1BB Costimulation in Chimeric Antigen Receptors Impedes T Cell Survival and Is Vector-Dependent. Cell Rep. 2017, 21, 17–26. [Google Scholar] [CrossRef] [Green Version]
- Jung, S.; Pluckthun, A. Improving in vivo folding and stability of a single-chain Fv antibody fragment by loop grafting. Protein Eng. Des. Sel. 1997, 10, 959–966. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Willuda, J.; Honegger, A.; Waibel, R.; Schubiger, P.A.; Stahel, R.; Zangemeister-Wittke, U.; Plückthun, A. High thermal stability is essential for tumor targeting of antibody fragments: Engineering of a humanized anti-epithelial glycoprotein-2 (epithelial cell adhesion molecule) single-chain Fv fragment. Cancer Res. 1999, 59, 5758–5767. [Google Scholar] [PubMed]
- Zajc, C.U.; Salzer, B.; Taft, J.M.; Reddy, S.T.; Lehner, M.; Traxlmayr, M.W. Driving CARs with alternative navigation tools–the potential of engineered binding scaffolds. Febs J. 2021, 288, 2103–2118. [Google Scholar] [CrossRef]
- Sommermeyer, D.; Hill, T.; Shamah, S.M.; Salter, A.I.; Chen, Y.; Mohler, K.M.; Riddell, S.R. Fully human CD19-specific chimeric antigen receptors for T-cell therapy. Leukemia 2017, 31, 2191–2199. [Google Scholar] [CrossRef] [Green Version]
- Roque, A.C.A.; Lowe, C.R.; Taipa, M.A. Antibodies and Genetically Engineered Related Molecules: Production and Purification. Biotechnol. Prog. 2004, 20, 639–654. [Google Scholar] [CrossRef]
- Ritter, G.; Cohen, L.S.; Williams, C.; Richards, E.C.; Old, L.J.; Welt, S. Serological analysis of human anti-human antibody responses in colon cancer patients treated with repeated doses of humanized monoclonal antibody A33. Cancer Res. 2001, 61, 6851–6859. [Google Scholar]
- Majzner, R.G.; Mackall, C.L. Tumor Antigen Escape from CAR T cell Therapy. Cancer Discov. 2018, 8, 1219–1226. [Google Scholar] [CrossRef] [Green Version]
- Maude, S.L.; Teachey, D.T.; Rheingold, S.R.; Shaw, P.A.; Aplenc, R.; Barrett, D.M.; Barker, C.S.; Callahan, C.; Frey, N.V.; Nazimuddin, F. Sustained remissions with CD19-specific chimeric antigen receptor (CAR)-modified T cells in children with relapsed/refractory ALL. J. Clin. Oncol. 2016, 34, 3011. [Google Scholar] [CrossRef]
- Maude, S.L.; Laetsch, T.W.; Buechner, J.; Rives, S.; Boyer, M.; Bittencourt, H.; Bader, P.; Verneris, M.R.; Stefanski, H.E.; Myers, G.D.; et al. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N. Engl. J. Med. 2018, 378, 439–448. [Google Scholar] [CrossRef]
- Gardner, R.; Wu, D.; Cherian, S.; Fang, M.; Hanafi, L.-A.; Finney, O.; Smithers, H.; Jensen, M.C.; Riddell, S.R.; Maloney, D.G.; et al. Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy. Blood 2016, 127, 2406–2410. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, D.W.; Kochenderfer, J.N.; Stetler-Stevenson, M.; Cui, Y.K.; Delbrook, C.; Feldman, S.A.; Fry, T.J.; Orentas, R.; Sabatino, M.; Shah, N.N.; et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: A phase 1 dose-escalation trial. Lancet 2015, 385, 517–528. [Google Scholar] [CrossRef]
- Lee III, D.W.; Stetler-Stevenson, M.; Yuan, C.M.; Shah, N.N.; Delbrook, C.; Yates, B.; Zhang, H.; Zhang, L.; Kochenderfer, J.N.; Rosenberg, S.A. Long-term outcomes following CD19 CAR T cell therapy for B-ALL are superior in patients receiving a fludarabine/cyclophosphamide preparative regimen and post-CAR hematopoietic stem cell transplantation. Blood 2016, 128, 218. [Google Scholar] [CrossRef]
- Park, J.H.; Rivière, I.; Gonen, M.; Wang, X.; Sénéchal, B.; Curran, K.J.; Sauter, C.; Wang, Y.; Santomasso, B.; Mead, E.; et al. Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N. Engl. J. Med. 2018, 378, 449–459. [Google Scholar] [CrossRef]
- Brown, C.E.; Badie, B.; Barish, M.E.; Weng, L.; Ostberg, J.R.; Chang, W.-C.; Naranjo, A.; Starr, R.; Wagner, J.; Wright, C.; et al. Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. Clin. Cancer Res. 2015, 21, 4062–4072. [Google Scholar] [CrossRef] [Green Version]
- Schmidts, A.; Ormhøj, M.; Choi, B.D.; Taylor, A.O.; Bouffard, A.A.; Scarfò, I.; Larson, R.C.; Frigault, M.J.; Gallagher, K.; Castano, A.P.; et al. Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma. Blood Adv. 2019, 3, 3248–3260. [Google Scholar] [CrossRef]
- Hudecek, M.; Lupo-Stanghellini, M.-T.; Kosasih, P.L.; Sommermeyer, D.; Jensen, M.C.; Rader, C.; Riddell, S.R. Receptor Affinity and Extracellular Domain Modifications Affect Tumor Recognition by ROR1-Specific Chimeric Antigen Receptor T Cells. Clin. Cancer Res. 2013, 19, 3153–3164. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chmielewski, M.; Hombach, A.; Heuser, C.; Adams, G.P.; Abken, H. T Cell Activation by Antibody-Like Immunoreceptors: Increase in Affinity of the Single-Chain Fragment Domain above Threshold Does Not Increase T Cell Activation against Antigen-Positive Target Cells but Decreases Selectivity. J. Immunol. 2004, 173, 7647–7653. [Google Scholar] [CrossRef]
- Ghorashian, S.; Kramer, A.M.; Onuoha, S.; Wright, G.; Bartram, J.; Richardson, R.; Albon, S.J.; Casanovas-Company, J.; Castro, F.; Popova, B.; et al. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. Nat. Med. 2019, 25, 1408–1414. [Google Scholar] [CrossRef] [PubMed]
- Roddie, C.; Dias, J.; O’Reilly, M.A.; Abbasian, M.; Cadinanos-Garai, A.; Vispute, K.; Bosshard-Carter, L.; Mitsikakou, M.; Mehra, V.; Roddy, H.; et al. Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia. J. Clin. Oncol. 2021. [Google Scholar] [CrossRef] [PubMed]
- Hasegawa, A.; Saito, S.; Narimatsu, S.; Nakano, S.; Nagai, M.; Ohnota, H.; Inada, Y.; Morokawa, H.; Nakashima, I.; Morita, D.; et al. Mutated GM-CSF-based CAR-T cells targeting CD116/CD131 complexes exhibit enhanced anti-tumor effects against acute myeloid leukaemia. Clin. Transl. Immunol. 2021, 10. [Google Scholar] [CrossRef] [PubMed]
- Zoine, J.T.; Prince, C.; Story, J.Y.; Branella, G.M.; Lytle, A.M.; Fedanov, A.; Alexander, J.S.; Porter, C.C.; Doering, C.B.; Spencer, H.T.; et al. Thrombopoietin-based CAR-T cells demonstrate in vitro and in vivo cytotoxicity to MPL positive acute myelogenous leukemia and hematopoietic stem cells. Gene 2021. [Google Scholar] [CrossRef]
- Brandt, C.S.; Baratin, M.; Yi, E.C.; Kennedy, J.; Gao, Z.; Fox, B.; Haldeman, B.; Ostrander, C.D.; Kaifu, T.; Chabannon, C.; et al. The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. J. Exp. Med. 2009, 206, 1495–1503. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Delahaye, N.F.; Rusakiewicz, S.; Martins, I.; Ménard, C.; Roux, S.; Lyonnet, L.; Paul, P.; Sarabi, M.; Chaput, N.; Semeraro, M.; et al. Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors. Nat. Med. 2011, 17, 700–707. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.; Wu, M.-R.; Sentman, C.L. An NKp30-Based Chimeric Antigen Receptor Promotes T Cell Effector Functions and Antitumor Efficacy In Vivo. J. Immunol. 2012, 189, 2290–2299. [Google Scholar] [CrossRef]
- Butler, S.E.; Brog, R.A.; Chang, C.H.; Sentman, C.L.; Huang, Y.H.; Ackerman, M.E. Engineering a natural ligand-based CAR: Directed evolution of the stress-receptor NKp30. Cancer Immunol. Immunother. 2021. [Google Scholar] [CrossRef] [PubMed]
- Wu, M.R.; Zhang, T.; Demars, L.R.; Sentman, C.L. B7H6-specific chimeric antigen receptors lead to tumor elimination and host antitumor immunity. Gene 2015, 22, 675–684. [Google Scholar] [CrossRef] [Green Version]
- Weiss, T.; Meister, H.; Weller, M.; Sentman, C.; Roth, P. PL2.1 Exploiting the DNAM-1 system for chimeric antigen receptor (CAR) T cell therapy of glioblastoma. Neuro Oncol. 2019, 21, iii2. [Google Scholar] [CrossRef]
- Zhang, T.; Lemoi, B.A.; Sentman, C.L. Chimeric NK-receptor–bearing T cells mediate antitumor immunotherapy. Blood 2005, 106, 1544–1551. [Google Scholar] [CrossRef]
- Barber, A.; Zhang, T.; Demars, L.R.; Conejo-Garcia, J.; Roby, K.F.; Sentman, C.L. Chimeric NKG2D Receptor–Bearing T Cells as Immunotherapy for Ovarian Cancer. Cancer Res. 2007, 67, 5003–5008. [Google Scholar] [CrossRef] [Green Version]
- Barber, A.; Meehan, K.R.; Sentman, C.L. Treatment of multiple myeloma with adoptively transferred chimeric NKG2D receptor-expressing T cells. Gene 2011, 18, 509–516. [Google Scholar] [CrossRef] [Green Version]
- Barber, A.; Zhang, T.; Megli, C.J.; Wu, J.; Meehan, K.R.; Sentman, C.L. Chimeric NKG2D receptor–expressing T cells as an immunotherapy for multiple myeloma. Exp. Hematol. 2008, 36, 1318–1328. [Google Scholar] [CrossRef] [Green Version]
- Zhang, T.; Barber, A.; Sentman, C.L. Chimeric NKG2D–Modified T Cells Inhibit Systemic T-Cell Lymphoma Growth in a Manner Involving Multiple Cytokines and Cytotoxic Pathways. Cancer Res. 2007, 67, 11029–11036. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Barber, A.; Sentman, C.L. Chimeric NKG2D T Cells Require Both T Cell- and Host-Derived Cytokine Secretion and Perforin Expression to Increase Tumor Antigen Presentation and Systemic Immunity. J. Immunol. 2009, 183, 2365–2372. [Google Scholar] [CrossRef] [Green Version]
- Spear, P.; Barber, A.; Rynda-Apple, A.; Sentman, C.L. Chimeric Antigen Receptor T Cells Shape Myeloid Cell Function within the Tumor Microenvironment through IFN-γ and GM-CSF. J. Immunol. 2012, 188, 6389–6398. [Google Scholar] [CrossRef] [PubMed]
- Barber, A.; Zhang, T.; Sentman, C.L. Immunotherapy with Chimeric NKG2D Receptors Leads to Long-Term Tumor-Free Survival and Development of Host Antitumor Immunity in Murine Ovarian Cancer. J. Immunol. 2008, 180, 72–78. [Google Scholar] [CrossRef] [Green Version]
- Spear, P.; Barber, A.; Sentman, C.L. Collaboration of chimeric antigen receptor (CAR)-expressing T cells and host T cells for optimal elimination of established ovarian tumors. Oncoimmunology 2013, 2, e23564. [Google Scholar] [CrossRef] [Green Version]
- Zhang, T.; Sentman, C.L. Mouse Tumor Vasculature Expresses NKG2D Ligands and Can Be Targeted by Chimeric NKG2D-Modified T Cells. J. Immunol. 2013, 190, 2455–2463. [Google Scholar] [CrossRef] [Green Version]
- Sentman, M.-L.; Murad, J.M.; Cook, W.J.; Wu, M.-R.; Reder, J.; Baumeister, S.H.; Dranoff, G.; Fanger, M.W.; Sentman, C.L. Mechanisms of Acute Toxicity in NKG2D Chimeric Antigen Receptor T Cell–Treated Mice. J. Immunol. 2016, 197, 4674–4685. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, T.; Barber, A.; Sentman, C.L. Generation of Antitumor Responses by Genetic Modification of Primary Human T Cells with a Chimeric NKG2D Receptor. Cancer Res. 2006, 66, 5927–5933. [Google Scholar] [CrossRef] [Green Version]
- Murad, J.M.; Baumeister, S.H.; Werner, L.; Daley, H.; Trébéden-Negre, H.; Reder, J.; Sentman, C.L.; Gilham, D.; Lehmann, F.; Snykers, S.; et al. Manufacturing development and clinical production of NKG2D chimeric antigen receptor–expressing T cells for autologous adoptive cell therapy. Cytotherapy 2018, 20, 952–963. [Google Scholar] [CrossRef]
- Baumeister, S.H.; Murad, J.; Werner, L.; Daley, H.; Trebeden-Negre, H.; Gicobi, J.K.; Schmucker, A.; Reder, J.; Sentman, C.L.; Gilham, D.E.; et al. Phase I Trial of Autologous CAR T Cells Targeting NKG2D Ligands in Patients with AML/MDS and Multiple Myeloma. Cancer Immunol. Res. 2019, 7, 100–112. [Google Scholar] [CrossRef] [PubMed]
- Shaffer, D.R.; Savoldo, B.; Yi, Z.; Chow, K.K.H.; Kakarla, S.; Spencer, D.M.; Dotti, G.; Wu, M.-F.; Liu, H.; Kenney, S.; et al. T cells redirected against CD70 for the immunotherapy of CD70-positive malignancies. Blood 2011, 117, 4304–4314. [Google Scholar] [CrossRef] [Green Version]
- Sauer, T.; Parikh, K.; Sharma, S.; Omer, B.; Sedloev, D.; Chen, Q.; Angenendt, L.; Schliemann, C.; Schmitt, M.; Müller-Tidow, C. CD70-specific CAR T cells have potent activity against Acute Myeloid Leukemia (AML) without HSC toxicity. Blood 2021, 138, 318–330. [Google Scholar] [CrossRef]
- Wang, Q.J.; Yu, Z.; Hanada, K.-I.; Patel, K.; Kleiner, D.; Restifo, N.P.; Yang, J.C. Preclinical Evaluation of Chimeric Antigen Receptors Targeting CD70-Expressing Cancers. Clin. Cancer Res. 2017, 23, 2267–2276. [Google Scholar] [CrossRef] [Green Version]
- CléMenceau, B.A.; Congy-Jolivet, N.; Gallot, G.R.; Vivien, R.G.; Gaschet, J.L.; Thibault, G.; Vié, H. Antibody-dependent cellular cytotoxicity (ADCC) is mediated by genetically modified antigen-specific human T lymphocytes. Blood 2006, 107, 4669–4677. [Google Scholar] [CrossRef] [Green Version]
- Ochi, F.; Fujiwara, H.; Tanimoto, K.; Asai, H.; Miyazaki, Y.; Okamoto, S.; Mineno, J.; Kuzushima, K.; Shiku, H.; Barrett, J.; et al. Gene-Modified Human α/β-T Cells Expressing a Chimeric CD16-CD3ζ Receptor as Adoptively Transferable Effector Cells for Anticancer Monoclonal Antibody Therapy. Cancer Immunol. Res. 2014, 2, 249–262. [Google Scholar] [CrossRef] [Green Version]
- Kudo, K.; Imai, C.; Lorenzini, P.; Kamiya, T.; Kono, K.; Davidoff, A.M.; Chng, W.J.; Campana, D. T Lymphocytes Expressing a CD16 Signaling Receptor Exert Antibody-Dependent Cancer Cell Killing. Cancer Res. 2014, 74, 93–103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- D’Aloia, M.M.; Caratelli, S.; Palumbo, C.; Battella, S.; Arriga, R.; Lauro, D.; Palmieri, G.; Sconocchia, G.; Alimandi, M. T lymphocytes engineered to express a CD16-chimeric antigen receptor redirect T-cell immune responses against immunoglobulin G–opsonized target cells. Cytotherapy 2016, 18, 278–290. [Google Scholar] [CrossRef] [PubMed]
- Han, X.; Cinay, G.E.; Zhao, Y.; Guo, Y.; Zhang, X.; Wang, P. Adnectin-Based Design of Chimeric Antigen Receptor for T Cell Engineering. Mol. Ther. 2017, 25, 2466–2476. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, Y.; Xu, Y.; Li, S.; Liu, J.; Xing, Y.; Xing, H.; Tian, Z.; Tang, K.; Rao, Q.; Wang, M.; et al. Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells. J. Hematol. Oncol. 2018, 11, 60. [Google Scholar] [CrossRef] [Green Version]
- Maiorova, V.; Mollaev, M.D.; Vikhreva, P.; Kulakovskaya, E.; Pershin, D.; Chudakov, D.M.; Kibardin, A.; Maschan, M.A.; Larin, S. Natural Flt3Lg-Based Chimeric Antigen Receptor (Flt3-CAR) T Cells Successfully Target Flt3 on AML Cell Lines. Vaccines 2021, 9, 1238. [Google Scholar] [CrossRef]
- Chen, N.; Xu, Y.; Mou, J.; Rao, Q.; Xing, H.; Tian, Z.; Tang, K.; Wang, M.; Wang, J. Targeting of IL-10R on acute myeloid leukemia blasts with chimeric antigen receptor-expressing T cells. Blood Cancer J. 2021, 11, 144. [Google Scholar] [CrossRef]
- Huang, G.; Yu, L.; Cooper, L.J.N.; Hollomon, M.; Huls, H.; Kleinerman, E.S. Genetically Modified T cells Targeting Interleukin-11 Receptor α-Chain Kill Human Osteosarcoma Cells and Induce the Regression of Established Osteosarcoma Lung Metastases. Cancer Res. 2012, 72, 271–281. [Google Scholar] [CrossRef] [Green Version]
- Kubo, H.; Yagyu, S.; Nakamura, K.; Yamashima, K.; Tomida, A.; Kikuchi, K.; Iehara, T.; Nakazawa, Y.; Hosoi, H. Development of non-viral, ligand-dependent, EPHB4-specific chimeric antigen receptor T cells for treatment of rhabdomyosarcoma. Mol. Ther.-Oncolytics 2021, 20, 646–658. [Google Scholar] [CrossRef]
- Ding, L.; Lamb, L.S. Abstract 1490: Dual chlorotoxin and methylguanine methyltransferase γδ-T cells for drug resistant immunotherapy of glioblastoma multiforme. Cancer Res. 2021, 81, 1490. [Google Scholar] [CrossRef]
- Kahlon, K.S.; Brown, C.; Cooper, L.J.N.; Raubitschek, A.; Forman, S.J.; Jensen, M.C. Specific Recognition and Killing of Glioblastoma Multiforme by Interleukin 13-Zetakine Redirected Cytolytic T Cells. Cancer Res. 2004, 64, 9160–9166. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brown, C.E.; Aguilar, B.; Starr, R.; Yang, X.; Chang, W.-C.; Weng, L.; Chang, B.; Sarkissian, A.; Brito, A.; Sanchez, J.F.; et al. Optimization of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells for Improved Anti-tumor Efficacy against Glioblastoma. Mol. Ther. 2018, 26, 31–44. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brown, C.E.; Alizadeh, D.; Starr, R.; Weng, L.; Wagner, J.R.; Naranjo, A.; Ostberg, J.R.; Blanchard, M.S.; Kilpatrick, J.; Simpson, J.; et al. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N. Engl. J. Med. 2016, 375, 2561–2569. [Google Scholar] [CrossRef]
- Alizadeh, D.; Wong, R.A.; Gholamin, S.; Maker, M.; Aftabizadeh, M.; Yang, X.; Pecoraro, J.R.; Jeppson, J.D.; Wang, D.; Aguilar, B.; et al. IFNγ Is Critical for CAR T Cell–Mediated Myeloid Activation and Induction of Endogenous Immunity. Cancer Discov. 2021, 11, 2248–2265. [Google Scholar] [CrossRef] [PubMed]
- Davies, D.M.; Foster, J.; Van Der Stegen, S.J.C.; Parente-Pereira, A.C.; Chiapero-Stanke, L.; Delinassios, G.J.; Burbridge, S.E.; Kao, V.; Liu, Z.; Bosshard-Carter, L.; et al. Flexible Targeting of ErbB Dimers That Drive Tumorigenesis by Using Genetically Engineered T Cells. Mol. Med. 2012, 18, 565–576. [Google Scholar] [CrossRef] [PubMed]
- Van Schalkwyk, M.C.; Papa, S.E.; Jeannon, J.-P.; Urbano, T.G.; Spicer, J.F.; Maher, J. Design of a phase I clinical trial to evaluate intratumoral delivery of ErbB-targeted chimeric antigen receptor T-cells in locally advanced or recurrent head and neck cancer. Hum. Gene Ther. Clin. Dev. 2013, 24, 134–142. [Google Scholar] [CrossRef]
- Larcombe-Young, D.; Papa, S.; Maher, J. PanErbB-targeted CAR T cell immunotherapy of head and neck cancer. Expert Opin. Biol. 2020, 20, 965–970. [Google Scholar] [CrossRef]
- Kosti, P.; Opzoomer, J.W.; Larios-Martinez, K.I.; Henley-Smith, R.; Scudamore, C.L.; Okesola, M.; Taher, M.Y.M.; Davies, D.M.; Muliaditan, T.; Larcombe-Young, D.; et al. Hypoxia-sensing CAR T cells provide safety and efficacy in treating solid tumors. Cell Rep. Med. 2021, 2, 100227. [Google Scholar] [CrossRef] [PubMed]
- Lee, L.; Draper, B.; Chaplin, N.; Philip, B.; Chin, M.; Galas-Filipowicz, D.; Onuoha, S.; Thomas, S.; Baldan, V.; Bughda, R.; et al. An APRIL-based chimeric antigen receptor for dual targeting of BCMA and TACI in multiple myeloma. Blood 2018, 131, 746–758. [Google Scholar] [CrossRef]
- Popat, R.; Zweegman, S.; Cavet, J.; Yong, K.; Lee, L.; Faulkner, J.; Kotsopoulou, E.; Al-Hajj, M.; Thomas, S.; Cordoba, S.P. Phase 1 first-in-human study of AUTO2, the first chimeric antigen receptor (CAR) T cell targeting APRIL for patients with relapsed/refractory multiple myeloma (RRMM). Blood 2019, 134, 3112. [Google Scholar] [CrossRef]
- Wang, D.; Starr, R.; Chang, W.-C.; Aguilar, B.; Alizadeh, D.; Wright, S.L.; Yang, X.; Brito, A.; Sarkissian, A.; Ostberg, J.R. Chlorotoxin-directed CAR T cells for specific and effective targeting of glioblastoma. Sci. Transl. Med. 2020, 12. [Google Scholar] [CrossRef] [PubMed]
- Park, S.; Shevlin, E.; Vedvyas, Y.; Zaman, M.; Park, S.; Hsu, Y.-M.S.; Min, I.M.; Jin, M.M. Micromolar affinity CAR T cells to ICAM-1 achieves rapid tumor elimination while avoiding systemic toxicity. Sci. Rep. 2017, 7, 14366. [Google Scholar] [CrossRef] [Green Version]
- Vedvyas, Y.; McCloskey, J.E.; Yang, Y.; Min, I.M.; Fahey, T.J.; Zarnegar, R.; Hsu, Y.-M.S.; Hsu, J.-M.; Van Besien, K.; Gaudet, I.; et al. Manufacturing and preclinical validation of CAR T cells targeting ICAM-1 for advanced thyroid cancer therapy. Sci. Rep. 2019, 9, 10634. [Google Scholar] [CrossRef] [Green Version]
- Jung, M.; Yang, Y.; McCloskey, J.E.; Zaman, M.; Vedvyas, Y.; Zhang, X.; Stefanova, D.; Gray, K.D.; Min, I.M.; Zarnegar, R.; et al. Chimeric Antigen Receptor T Cell Therapy Targeting ICAM-1 in Gastric Cancer. Mol. Oncolytics 2020, 18, 587–601. [Google Scholar] [CrossRef] [PubMed]
- Urbanska, K.; Stashwick, C.; Poussin, M.; Powell, D.J. Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer. Cancer Immunol. Res. 2015, 3, 1130–1137. [Google Scholar] [CrossRef] [Green Version]
- Perales-Puchalt, A.; Svoronos, N.; Rutkowski, M.R.; Allegrezza, M.J.; Tesone, A.J.; Payne, K.K.; Wickramasinghe, J.; Nguyen, J.M.; O’Brien, S.W.; Gumireddy, K.; et al. Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target. Clin. Cancer Res. 2017, 23, 441–453. [Google Scholar] [CrossRef] [Green Version]
- Nakazawa, Y.; Matsuda, K.; Kurata, T.; Sueki, A.; Tanaka, M.; Sakashita, K.; Imai, C.; Wilson, M.H.; Koike, K. Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34+ cells of juvenile myelomonocytic leukemia. J. Hematol. Oncol. 2016, 9, 27. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lipovsek, D. Adnectins: Engineered target-binding protein therapeutics. Protein Eng. Des. Sel. 2011, 24, 3–9. [Google Scholar] [CrossRef] [Green Version]
- Hackel, B.J.; Ackerman, M.E.; Howland, S.W.; Wittrup, K.D. Stability and CDR Composition Biases Enrich Binder Functionality Landscapes. J. Mol. Biol. 2010, 401, 84–96. [Google Scholar] [CrossRef] [Green Version]
- Weidle, U.H.; Auer, J.; Brinkmann, U.; Georges, G.; Tiefenthaler, G. The emerging role of new protein scaffold-based agents for treatment of cancer. Cancer Genom. Proteom. 2013, 10, 155–168. [Google Scholar]
- Nicholson, R.I.; Gee, J.M.W.; Harper, M.E. EGFR and cancer prognosis. Eur. J. Cancer 2001, 37, 9–15. [Google Scholar] [CrossRef]
- Kottaridis, P.D.; Gale, R.E.; Frew, M.E.; Harrison, G.; Langabeer, S.E.; Belton, A.A.; Walker, H.; Wheatley, K.; Bowen, D.T.; Burnett, A.K.; et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: Analysis of 854 patients from the United King. Blood 2001, 98, 1752–1759. [Google Scholar] [CrossRef] [PubMed]
- Gilliland, D.G.; Griffin, J.D. The roles of FLT3 in hematopoiesis and leukemia. Blood 2002, 100, 1532–1542. [Google Scholar] [CrossRef] [Green Version]
- Kantarjian, H. Acute myeloid leukemia-Major progress over four decades and glimpses into the future. Am. J. Hematol. 2016, 91, 131–145. [Google Scholar] [CrossRef] [Green Version]
- Kikushige, Y.; Yoshimoto, G.; Miyamoto, T.; Iino, T.; Mori, Y.; Iwasaki, H.; Niiro, H.; Takenaka, K.; Nagafuji, K.; Harada, M.; et al. Human Flt3 Is Expressed at the Hematopoietic Stem Cell and the Granulocyte/Macrophage Progenitor Stages to Maintain Cell Survival. J. Immunol. 2008, 180, 7358–7367. [Google Scholar] [CrossRef] [Green Version]
- Wetzler, M.; Baer, M.R.; Bernstein, S.H.; Blumenson, L.; Stewart, C.; Barcos, M.; Mrózek, K.; Block, A.; Herzig, G.P.; Bloomfield, C.D. Expression of c-mpl mRNA, the receptor for thrombopoietin, in acute myeloid leukemia blasts identifies a group of patients with poor response to intensive chemotherapy. J. Clin. Oncol. 1997, 15, 2262–2268. [Google Scholar] [CrossRef]
- Albitar, M.; Manshouri, T.; Kantarjian, H.; Keating, M.; Estrov, Z.; Faber, J.; Freireich, E.J.; Pierce, S.; Estey, E. Correlation between lower c-mpl protein expression and favorable cytogenetic groups in acute myeloid leukemia. Leuk. Res. 1999, 23, 63–69. [Google Scholar] [CrossRef]
- Fox, N.; Priestley, G.; Papayannopoulou, T.; Kaushansky, K. Thrombopoietin expands hematopoietic stem cells after transplantation. J. Clin. Investig. 2002, 110, 389–394. [Google Scholar] [CrossRef]
- Kaushansky, K.; Lok, S.; Holly, R.D.; Broudy, V.C.; Lin, N.; Bailey, M.C.; Forstrom, J.W.; Buddle, M.M.; Oort, P.J.; Hagen, F.S. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature 1994, 369, 568–571. [Google Scholar] [CrossRef] [PubMed]
- Yoshihara, H.; Arai, F.; Hosokawa, K.; Hagiwara, T.; Takubo, K.; Nakamura, Y.; Gomei, Y.; Iwasaki, H.; Matsuoka, S.; Miyamoto, K. Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche. Cell Stem Cell 2007, 1, 685–697. [Google Scholar] [CrossRef] [Green Version]
- Yogarajah, M.; Tefferi, A. Leukemic Transformation in Myeloproliferative Neoplasms. Mayo Clin. Proc. 2017, 92, 1118–1128. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pende, D.; Spaggiari, G.M.; Marcenaro, S.; Martini, S.; Rivera, P.; Capobianco, A.; Falco, M.; Lanino, E.; Pierri, I.; Zambello, R.; et al. Analysis of the receptor-ligand interactions in the natural killer–mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: Evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112). Blood 2005, 105, 2066–2073. [Google Scholar] [CrossRef] [PubMed]
- Carlsten, M.; Norell, H.; Bryceson, Y.T.; Poschke, I.; Schedvins, K.; Ljunggren, H.-G.; Kiessling, R.; Malmberg, K.-J. Primary Human Tumor Cells Expressing CD155 Impair Tumor Targeting by Down-Regulating DNAM-1 on NK Cells. J. Immunol. 2009, 183, 4921–4930. [Google Scholar] [CrossRef] [Green Version]
- Castriconi, R.; Dondero, A.; Corrias, M.V.; Lanino, E.; Pende, D.; Moretta, L.; Bottino, C.; Moretta, A. Natural Killer Cell-Mediated Killing of Freshly Isolated Neuroblastoma Cells. Cancer Res. 2004, 64, 9180–9184. [Google Scholar] [CrossRef] [Green Version]
- Lakshmikanth, T.; Burke, S.; Ali, T.H.; Kimpfler, S.; Ursini, F.; Ruggeri, L.; Capanni, M.; Umansky, V.; Paschen, A.; Sucker, A.; et al. NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. J. Clin. Investig. 2009, 119, 1251–1263. [Google Scholar] [CrossRef] [Green Version]
- Castriconi, R.; Daga, A.; Dondero, A.; Zona, G.; Poliani, P.L.; Melotti, A.; Griffero, F.; Marubbi, D.; Spaziante, R.; Bellora, F.; et al. NK Cells Recognize and Kill Human Glioblastoma Cells with Stem Cell-Like Properties. J. Immunol. 2009, 182, 3530–3539. [Google Scholar] [CrossRef] [Green Version]
- Wu, M.-R.; Zhang, T.; Alcon, A.; Sentman, C.L. DNAM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma. Cancer Immunol. Immunother. 2015, 64, 409–418. [Google Scholar] [CrossRef] [Green Version]
- Kučan Brlić, P.; Lenac Roviš, T.; Cinamon, G.; Tsukerman, P.; Mandelboim, O.; Jonjić, S. Targeting PVR (CD155) and its receptors in anti-tumor therapy. Cell. Mol. Immunol. 2019, 16, 40–52. [Google Scholar] [CrossRef] [Green Version]
- Bouchard, M.J.; Dong, Y.; McDermott, B.M.; Lam, D.-H.; Brown, K.R.; Shelanski, M.; Bellvé, A.R.; Racaniello, V.R. Defects in Nuclear and Cytoskeletal Morphology and Mitochondrial Localization in Spermatozoa of Mice Lacking Nectin-2, a Component of Cell-Cell Adherens Junctions. Mol. Cell. Biol. 2000, 20, 2865–2873. [Google Scholar] [CrossRef] [Green Version]
- Takai, Y.; Nakanishi, H. Nectin and afadin: Novel organizers of intercellular junctions. J. Cell Sci. 2003, 116, 17–27. [Google Scholar] [CrossRef] [Green Version]
- Randolph, M.E.; Cleary, M.M.; Bajwa, Z.; Svalina, M.N.; Young, M.C.; Mansoor, A.; Kaur, P.; Bult, C.J.; Goros, M.W.; Michalek, J.E.; et al. EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma. PLoS ONE 2017, 12, e0183161. [Google Scholar] [CrossRef] [Green Version]
- Noren, N.K.; Lu, M.; Freeman, A.L.; Koolpe, M.; Pasquale, E.B. Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor growth. Proc. Natl. Acad. Sci. USA 2004, 101, 5583–5588. [Google Scholar] [CrossRef] [Green Version]
- Aslam, M.I.; Abraham, J.; Mansoor, A.; Druker, B.J.; Tyner, J.W.; Keller, C. PDGFR reverses EphB4 signaling in alveolar rhabdomyosarcoma. Proc. Natl. Acad. Sci. USA 2014, 111, 6383–6388. [Google Scholar] [CrossRef] [Green Version]
- Cerwenka, A.; Lanier, L.L. Ligands for natural killer cell receptors: Redundancy or specificity. Immunol. Rev. 2001, 181, 158–169. [Google Scholar] [CrossRef]
- Wensveen, F.M.; Jelenčić, V.; Polić, B. NKG2D: A master regulator of immune cell responsiveness. Front. Immunol. 2018, 9, 441. [Google Scholar] [CrossRef]
- Raulet, D.H. Roles of the NKG2D immunoreceptor and its ligands. Nat. Rev. Immunol. 2003, 3, 781–790. [Google Scholar] [CrossRef]
- Wu, J.D.; Higgins, L.M.; Steinle, A.; Cosman, D.; Haugk, K.; Plymate, S.R. Prevalent expression of the immunostimulatory MHC class I chain–related molecule is counteracted by shedding in prostate cancer. J. Clin. Investig. 2004, 114, 560–568. [Google Scholar] [CrossRef]
- Groh, V.; Rhinehart, R.; Secrist, H.; Bauer, S.; Grabstein, K.H.; Spies, T. Broad tumor-associated expression and recognition by tumor-derived T cells of MICA and MICB. Proc. Natl. Acad. Sci. USA 1999, 96, 6879–6884. [Google Scholar] [CrossRef] [Green Version]
- Dhar, P.; Wu, J.D. NKG2D and its ligands in cancer. Curr. Opin. Immunol. 2018, 51, 55–61. [Google Scholar] [CrossRef]
- Brown, C.E.; Warden, C.D.; Starr, R.; Deng, X.; Badie, B.; Yuan, Y.-C.; Forman, S.J.; Barish, M.E. Glioma IL13Rα2 Is Associated with Mesenchymal Signature Gene Expression and Poor Patient Prognosis. PLoS ONE 2013, 8, e77769. [Google Scholar] [CrossRef]
- Debinski, W.; Gibo, D.M.; Obiri, N.I.; Kealiher, A.; Puri, R.K. Novel anti–brain tumor cytotoxins specific for cancer cells. Nat. Biotechnol. 1998, 16, 449–453. [Google Scholar] [CrossRef]
- Hynes, N.E.; Macdonald, G. ErbB receptors and signaling pathways in cancer. Curr. Opin. Cell Biol. 2009, 21, 177–184. [Google Scholar] [CrossRef]
- Morgan, S.; Grandis, J.R. ErbB receptors in the biology and pathology of the aerodigestive tract. Exp. Cell Res. 2009, 315, 572–582. [Google Scholar] [CrossRef] [Green Version]
- Rogers, S.J.; Harrington, K.J.; Rhys-Evans, P.; O-Charoenrat, P.; Eccles, S.A. Biological significance of c-erbB family oncogenes in head and neck cancer. Cancer Metastasis Rev. 2005, 24, 47–69. [Google Scholar] [CrossRef]
- Holbro, T.; Beerli, R.R.; Maurer, F.; Koziczak, M.; Barbas, C.F.; Hynes, N.E. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc. Natl. Acad. Sci. USA 2003, 100, 8933–8938. [Google Scholar] [CrossRef] [Green Version]
- Hirsch, F.R.; Varella-Garcia, M.; Cappuzzo, F. Predictive value of EGFR and HER2 overexpression in advanced non-small-cell lung cancer. Oncogene 2009, 28, S32–S37. [Google Scholar] [CrossRef] [Green Version]
- Erjala, K.; Sundvall, M.; Junttila, T.T.; Zhang, N.; Savisalo, M.; Mali, P.; Kulmala, J.; Pulkkinen, J.; Grenman, R.; Elenius, K. Signaling via ErbB2 and ErbB3 Associates with Resistance and Epidermal Growth Factor Receptor (EGFR) Amplification with Sensitivity to EGFR Inhibitor Gefitinib in Head and Neck Squamous Cell Carcinoma Cells. Clin. Cancer Res. 2006, 12, 4103–4111. [Google Scholar] [CrossRef] [Green Version]
- Wilkie, S.; Burbridge, S.E.; Chiapero-Stanke, L.; Pereira, A.C.P.; Cleary, S.; Van Der Stegen, S.J.C.; Spicer, J.F.; Davies, D.M.; Maher, J. Selective Expansion of Chimeric Antigen Receptor-targeted T-cells with Potent Effector Function using Interleukin-4. J. Biol. Chem. 2010, 285, 25538–25544. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morgan, R.A.; Yang, J.C.; Kitano, M.; Dudley, M.E.; Laurencot, C.M.; Rosenberg, S.A. Case Report of a Serious Adverse Event Following the Administration of T Cells Transduced With a Chimeric Antigen Receptor Recognizing ERBB2. Mol. Ther. 2010, 18, 843–851. [Google Scholar] [CrossRef]
- Novak, A.J.; Darce, J.R.; Arendt, B.K.; Harder, B.; Henderson, K.; Kindsvogel, W.; Gross, J.A.; Greipp, P.R.; Jelinek, D.F. Expression of BCMA, TACI, and BAFF-R in multiple myeloma: A mechanism for growth and survival. Blood 2004, 103, 689–694. [Google Scholar] [CrossRef] [Green Version]
- Lyons, S.A.; O’Neal, J.; Sontheimer, H. Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia 2002, 39, 162–173. [Google Scholar] [CrossRef] [PubMed]
- Soroceanu, L.; Gillespie, Y.; Khazaeli, M.; Sontheimer, H. Use of chlorotoxin for targeting of primary brain tumors. Cancer Res. 1998, 58, 4871–4879. [Google Scholar] [PubMed]
- Mamelak, A.N.; Rosenfeld, S.; Bucholz, R.; Raubitschek, A.; Nabors, L.B.; Fiveash, J.B.; Shen, S.; Khazaeli, M.B.; Colcher, D.; Liu, A.; et al. Phase I Single-Dose Study of Intracavitary-Administered Iodine-131-TM-601 in Adults With Recurrent High-Grade Glioma. J. Clin. Oncol. 2006, 24, 3644–3650. [Google Scholar] [CrossRef]
- Parrish-Novak, J.; Byrnes-Blake, K.; Lalayeva, N.; Burleson, S.; Fidel, J.; Gilmore, R.; Gayheart-Walsten, P.; Bricker, G.A.; Crumb, W.J.; Tarlo, K.S.; et al. Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent. Int. J. Toxicol. 2017, 36, 104–112. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yamada, M.; Miller, D.M.; Lowe, M.; Rowe, C.; Wood, D.; Soyer, H.P.; Byrnes-Blake, K.; Parrish-Novak, J.; Ishak, L.; Olson, J.M. A first-in-human study of BLZ-100 (tozuleristide) demonstrates tolerability and safety in skin cancer patients. Contemp. Clin. Trials Commun. 2021, 23, 100830. [Google Scholar] [CrossRef]
- Deshane, J.; Garner, C.C.; Sontheimer, H. Chlorotoxin Inhibits Glioma Cell Invasion via Matrix Metalloproteinase-2. J. Biol. Chem. 2003, 278, 4135–4144. [Google Scholar] [CrossRef] [Green Version]
- Reina, M.; Espel, E. Role of LFA-1 and ICAM-1 in Cancer. Cancers 2017, 9, 153. [Google Scholar] [CrossRef] [Green Version]
- Simoni, M.; Gromoll, J.R.; Nieschlag, E. The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology. Endocr. Rev. 1997, 18, 739–773. [Google Scholar] [CrossRef] [Green Version]
- Van Deusen, K.E.; Rajapakse, R.; Bullock, T.N.J. CD70 expression by dendritic cells plays a critical role in the immunogenicity of CD40-independent, CD4+ T cell-dependent, licensed CD8+ T cell responses. J. Leukoc. Biol. 2010, 87, 477–485. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- O’Neill, R.E.; Du, W.; Mohammadpour, H.; Alqassim, E.; Qiu, J.; Chen, G.; McCarthy, P.L.; Lee, K.P.; Cao, X. T Cell–Derived CD70 Delivers an Immune Checkpoint Function in Inflammatory T Cell Responses. J. Immunol. 2017, 199, 3700–3710. [Google Scholar] [CrossRef] [Green Version]
- Arens, R.; Nolte, M.A.; Tesselaar, K.; Heemskerk, B.; Reedquist, K.A.; Van Lier, R.A.W.; Van Oers, M.H.J. Signaling through CD70 Regulates B Cell Activation and IgG Production. J. Immunol. 2004, 173, 3901–3908. [Google Scholar] [CrossRef] [Green Version]
- Lens, S.M.A.; Drillenburg, P.; Den Drijver, B.F.A.; Van Schijndel, G.; Pals, S.T.; Van Lier, R.A.W.; Van Oers, M.H.J. Aberrant expression and reverse signalling of CD70 on malignant B cells. Br. J. Haematol. 1999, 106, 491–503. [Google Scholar] [CrossRef]
- Baba, M.; Okamoto, M.; Hamasaki, T.; Horai, S.; Wang, X.; Ito, Y.; Suda, Y.; Arima, N. Highly Enhanced Expression of CD70 on Human T-Lymphotropic Virus Type 1-Carrying T-Cell Lines and Adult T-Cell Leukemia Cells. J. Virol. 2008, 82, 3843–3852. [Google Scholar] [CrossRef] [Green Version]
- Jilaveanu, L.B.; Sznol, J.; Aziz, S.A.; Duchen, D.; Kluger, H.M.; Camp, R.L. CD70 expression patterns in renal cell carcinoma. Hum. Pathol. 2012, 43, 1394–1399. [Google Scholar] [CrossRef] [Green Version]
- Chahlavi, A.; Rayman, P.; Richmond, A.L.; Biswas, K.; Zhang, R.; Vogelbaum, M.; Tannenbaum, C.; Barnett, G.; Finke, J.H. Glioblastomas Induce T-Lymphocyte Death by Two Distinct Pathways Involving Gangliosides and CD70. Cancer Res. 2005, 65, 5428–5438. [Google Scholar] [CrossRef] [Green Version]
- Lanza, F.; Castagnari, B.; Rigolin, G.; Moretti, S.; Latorraca, A.; Ferrari, L.; Bardi, A.; Castoldi, G. Flow cytometry measurement of GM-CSF receptors in acute leukemic blasts, and normal hemopoietic cells. Leukemia 1997, 11, 1700–1710. [Google Scholar] [CrossRef] [Green Version]
- Lopez, A.F.; Shannon, M.F.; Hercus, T.; Nicola, N.A.; Cambareri, B.; Dottore, M.; Layton, M.J.; Eglinton, L.; Vadas, M.A. Residue 21 of human granulocyte-macrophage colony-stimulating factor is critical for biological activity and for high but not low affinity binding. Embo J. 1992, 11, 909–916. [Google Scholar] [CrossRef]
- Hercus, T.R.; Bagley, C.J.; Cambareri, B.; Dottore, M.; Woodcock, J.M.; Vadas, M.A.; Shannon, M.F.; Lopez, A.F. Specific human granulocyte-macrophage colony-stimulating factor antagonists. Proc. Natl. Acad. Sci. USA 1994, 91, 5838–5842. [Google Scholar] [CrossRef] [Green Version]
- Lo Nigro, C.; Macagno, M.; Sangiolo, D.; Bertolaccini, L.; Aglietta, M.; Merlano, M.C. NK-mediated antibody-dependent cell-mediated cytotoxicity in solid tumors: Biological evidence and clinical perspectives. Ann. Transl. Med. 2019, 7, 105. [Google Scholar] [CrossRef] [Green Version]
- Yeap, W.H.; Wong, K.L.; Shimasaki, N.; Teo, E.C.Y.; Quek, J.K.S.; Yong, H.X.; Diong, C.P.; Bertoletti, A.; Linn, Y.C.; Wong, S.C. CD16 is indispensable for antibody-dependent cellular cytotoxicity by human monocytes. Sci. Rep. 2016, 6, 34310. [Google Scholar] [CrossRef]
- Vera, J.; Savoldo, B.; Vigouroux, S.; Biagi, E.; Pule, M.; Rossig, C.; Wu, J.; Heslop, H.E.; Rooney, C.M.; Brenner, M.K.; et al. T lymphocytes redirected against the κ light chain of human immunoglobulin efficiently kill mature B lymphocyte-derived malignant cells. Blood 2006, 108, 3890–3897. [Google Scholar] [CrossRef] [Green Version]
Receptor Antigen | Ligand | Indication | Phase of Development | Clinical Trial | Status | Ref | |
---|---|---|---|---|---|---|---|
Natural receptor-based CAR T cells | B7H6 | NKp30 | various | Preclinical | [66,67] | ||
DNAM-1 | PVR, Nectin-2 | various | Preclinical | [68,69] | |||
NKG2D | MICA, MICB, ULBP1-6 | various | Clinical | NCT02203825 NCT03018405 NCT03310008 NCT03612739 NCT03466320 NCT04167696 NCT03692429 NCT04991948 | Completed Unknown Active Withdrawn Completed Recruiting Recruiting Recruiting | [70,71,72,73,74,75,76,77,78,79,80,81,82,83] | |
CD27 | CD70 | various | Clinical | NCT02830724 | Suspended | [84,85,86] | |
CD16 | Fc | various | Clinical | NCT02776813 NCT03266692 NCT03189836 NCT03680560 NCT02840110 | Completed Terminated Terminated Terminated Terminated | [87,88,89,90] | |
Ligand-based CAR T cells | EGFR | E3 Adnectin | Solid tumors | Preclinical | [91] | ||
FLT3 | FLT3L | AML | Preclinical | [92,93] | |||
IL-10R | IL-10 | AML | Preclinical | [94] | |||
MPL | TPO | AML | Preclinical | [63] | |||
IL-11Rα | IL-11 | OS | Preclinical | [95] | |||
EPHB4 | EPHRIN B2 | RMS | Preclinical | [96] | |||
unknown | CTLX | GBM | Preclinical | [97] | |||
IL-13Rα2 | E13Y IL-13 | GBM | Clinical | NCT02208362 NCT04003649 NCT04510051 NCT04661384 | Recruiting Recruiting Recruiting Recruiting | [56,98,99,100,101] | |
ErbB family | T1E | HNSCC | Clinical | NCT01818323 | Recruiting | [102,103,104,105] | |
BCMA, TACI | APRIL | MM | Clinical | NCT03287804 NCT04657861 | Terminated Not yet recruiting | [106,107] | |
BCMA, TACI | TriPRIL | MM | Clinical | NCT05020444 | Recruiting | [57] | |
unknown | CTLX | GBM | Clinical | NCT04214392 | Recruiting | [108] | |
ICAM-I | LFA-1 | Thyroid | Clinical | NCT04420754 | Recruiting | [109,110,111] | |
FSHR | FSH | Ovarian | Clinical | [112,113] | |||
GMR | GM-CSF | AML, JMML | Clinical | jRCT2033210029 | Recruiting | [62,114] |
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Branella, G.M.; Spencer, H.T. Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing. Cells 2022, 11, 21. https://doi.org/10.3390/cells11010021
Branella GM, Spencer HT. Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing. Cells. 2022; 11(1):21. https://doi.org/10.3390/cells11010021
Chicago/Turabian StyleBranella, Gianna M., and Harold Trent Spencer. 2022. "Natural Receptor- and Ligand-Based Chimeric Antigen Receptors: Strategies Using Natural Ligands and Receptors for Targeted Cell Killing" Cells 11, no. 1: 21. https://doi.org/10.3390/cells11010021