Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo
Abstract
:1. Introduction
2. Results
2.1. Preparation and Characterization of Apt-HJ
2.2. Serum Stability of Apt-HJ
2.3. Affinity of Apt-HJ to Target Cancer Cells
2.4. In Vivo Antitumor Study
3. Discussion
4. Materials and Methods
4.1. Cells and Cultures
4.2. Synthesis of PD-L1 Aptamer
4.3. Preparation of Apt-HJ
4.4. Characterization of Apt-HJ
4.5. Serum Stability of Apt-HJ
4.6. Evaluation of Cellular Binding Capacity
4.7. Confocal Imaging Studies
4.8. In Vivo Antitumor Study
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Sample Availability
References
- Li, Z.; Song, W.; Rubinstein, M.; Liu, D. Recent updates in cancer immunotherapy: A comprehensive review and perspective of the 2018 China Cancer Immunotherapy Workshop in Beijing. J. Hematol. Oncol. 2018, 11, 142. [Google Scholar]
- Pardoll, D.M. The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012, 12, 252–264. [Google Scholar]
- Khalil, D.N.; Smith, E.L.; Brentjens, R.J.; Wolchok, J.D. The future of cancer treatment: Immunomodulation, CARs and combination immunotherapy. Nat. Rev. Clin. Oncol. 2016, 13, 273–290. [Google Scholar]
- Ahmadzadeh, M.; Johnson, L.A.; Heemskerk, B.; Wunderlich, J.R.; Dudley, M.E.; White, D.E.; Rosenberg, S.A. Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 2009, 114, 1537–1544. [Google Scholar]
- Francisco, L.M.; Sage, P.T.; Sharpe, A.H. The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev. 2010, 236, 219–242. [Google Scholar]
- Salmaninejad, A.; Valilou, S.F.; Shabgah, A.G.; Aslani, S.; Alimardani, M.; Pasdar, A.; Sahebkar, A. PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy. J. Cell. Physiol. 2019, 234, 16824–16837. [Google Scholar]
- Iwai, Y.; Ishida, M.; Tanaka, Y.; Okazaki, T.; Honjo, T.; Minato, N. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. USA 2002, 99, 12293–12297. [Google Scholar]
- Akinleye, A.; Rasool, Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J. Hematol. Oncol. 2019, 12, 92. [Google Scholar]
- Pandha, H.; Pawelec, G. Immune checkpoint targeting as anti-cancer immunotherapy: Promises, questions, challenges and the need for predictive biomarkers at ASCO 2015. Cancer Immunol. Immunother. 2015, 64, 1071–1074. [Google Scholar]
- Kantoff, P.W.; Higano, C.S.; Shore, N.D.; Berger, E.R.; Small, E.J.; Penson, D.F.; Redfern, C.H.; Ferrari, A.C.; Dreicer, R.; Sims, R.B.; et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N. Engl. J. Med. 2010, 363, 411–422. [Google Scholar]
- Robert, C.; Long, G.V.; Brady, B.; Dutriaux, C.; Maio, M.; Mortier, L.; Hassel, J.C.; Rutkowski, P.; McNeil, C.; Kalinka-Warzocha, E.; et al. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 2015, 372, 320–330. [Google Scholar]
- Robert, C.; Schachter, J.; Long, G.V.; Arance, A.; Grob, J.J.; Mortier, L.; Daud, A.; Carlino, M.S.; McNeil, C.; Lotem, M.; et al. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N. Engl. J. Med. 2015, 372, 2521–2532. [Google Scholar]
- Robert, C.; Ribas, A.; Hamid, O.; Daud, A.; Wolchok, J.D.; Joshua, A.M.; Hwu, W.J.; Weber, J.S.; Gangadhar, T.C.; Joseph, R.W.; et al. Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma. J. Clin. Oncol. 2018, 36, 1668–1674. [Google Scholar]
- Brahmer, J.; Reckamp, K.L.; Baas, P.; Crinò, L.; Eberhardt, W.E.; Poddubskaya, E.; Antonia, S.; Pluzanski, A.; Vokes, E.E.; Holgado, E.; et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N. Engl. J. Med. 2015, 373, 123–135. [Google Scholar]
- Gong, J.; Chehrazi-Raffle, A.; Reddi, S.; Salgia, R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: A comprehensive review of registration trials and future considerations. J. Immunother. Cancer 2018, 6, 8. [Google Scholar]
- Harding, F.A.; Stickler, M.M.; Razo, J.; DuBridge, R.B. The immunogenicity of humanized and fully human antibodies: Residual immunogenicity resides in the CDR regions. MAbs 2010, 2, 256–265. [Google Scholar]
- Vaisman-Mentesh, A.; Gutierrez-Gonzalez, M.; DeKosky, B.J.; Wine, Y. The Molecular Mechanisms That Underlie the Immune Biology of Anti-drug Antibody Formation Following Treatment With Monoclonal Antibodies. Front. Immunol. 2020, 11, 1951. [Google Scholar]
- Zhao, N.; Pei, S.N.; Qi, J.; Zeng, Z.; Iyer, S.P.; Lin, P.; Tung, C.H.; Zu, Y. Oligonucleotide aptamer-drug conjugates for targeted therapy of acute myeloid leukemia. Biomaterials 2015, 67, 42–51. [Google Scholar]
- Wu, J.; Song, C.; Jiang, C.; Shen, X.; Qiao, Q.; Hu, Y. Nucleolin targeting AS1411 modified protein nanoparticle for antitumor drugs delivery. Mol. Pharm. 2013, 10, 3555–3563. [Google Scholar]
- Chen, Y.; Wang, J.; Wang, J.; Wang, L.; Tan, X.; Tu, K.; Tong, X.; Qi, L. Aptamer Functionalized Cisplatin-Albumin Nanoparticles for Targeted Delivery to Epidermal Growth Factor Receptor Positive Cervical Cancer. J. Biomed. Nanotechnol. 2016, 12, 656–666. [Google Scholar]
- Zhang, Y.; Lai, B.S.; Juhas, M. Recent Advances in Aptamer Discovery and Applications. Molecules 2019, 24, 941. [Google Scholar]
- Stein, C.A.; Castanotto, D. FDA-Approved Oligonucleotide Therapies in 2017. Mol. Ther. 2017, 25, 1069–1075. [Google Scholar]
- Lai, W.Y.; Huang, B.T.; Wang, J.W.; Lin, P.Y.; Yang, P.C. A Novel PD-L1-targeting Antagonistic DNA Aptamer With Antitumor Effects. Mol. Ther. Nucleic Acids 2016, 5, e397. [Google Scholar]
- Zhou, G.; Latchoumanin, O.; Hebbard, L.; Duan, W.; Liddle, C.; George, J.; Qiao, L. Aptamers as targeting ligands and therapeutic molecules for overcoming drug resistance in cancers. Adv. Drug Deliv. Rev. 2018, 134, 107–121. [Google Scholar]
- Tang, S.; Chen, M.; Zheng, N. Sub-10-nm Pd nanosheets with renal clearance for efficient near-infrared photothermal cancer therapy. Small 2014, 10, 3139–3144. [Google Scholar]
- Duangrat, R.; Udomprasert, A.; Kangsamaksin, T. Tetrahedral DNA nanostructures as drug delivery and bioimaging platforms in cancer therapy. Cancer Sci. 2020, 111, 3164–3173. [Google Scholar]
- Linko, V.; Ora, A.; Kostiainen, M.A. DNA Nanostructures as Smart Drug-Delivery Vehicles and Molecular Devices. Trends Biotechnol. 2015, 33, 586–594. [Google Scholar]
- Kobayashi, H.; Watanabe, R.; Choyke, P.L. Improving conventional enhanced permeability and retention (EPR) effects; what is the appropriate target? Theranostics 2013, 4, 81–89. [Google Scholar]
- Deleavey, G.F.; Damha, M.J. Designing chemically modified oligonucleotides for targeted gene silencing. Chem. Biol. 2012, 19, 937–954. [Google Scholar]
- Watts, J.K.; Corey, D.R. Silencing disease genes in the laboratory and the clinic. J. Pathol. 2012, 226, 365–379. [Google Scholar]
- Eckstein, F. Phosphorothioates, essential components of therapeutic oligonucleotides. Nucleic Acid Ther. 2014, 24, 374–387. [Google Scholar]
- Spitzer, S.; Eckstein, F. Inhibition of deoxyribonucleases by phosphorothioate groups in oligodeoxyribonucleotides. Nucleic Acids Res. 1988, 16, 11691–11704. [Google Scholar]
- Zhou, J.; Rossi, J. Aptamers as targeted therapeutics: Current potential and challenges. Nat. Rev. Drug Discov. 2017, 16, 181–202. [Google Scholar]
- Zhang, F.; Liu, M.R.; Wan, H.T. Discussion about several potential drawbacks of PEGylated therapeutic proteins. Biol. Pharm. Bull. 2014, 37, 335–339. [Google Scholar]
- Geleijnse, M.L.; Nemes, A.; Vletter, W.B.; Michels, M.; Soliman, O.I.; Caliskan, K.; Galema, T.W.; ten Cate, F.J. Adverse reactions after the use of sulphur hexafluoride (SonoVue) echo contrast agent. J. Cardiovasc. Med. 2009, 10, 75–77. [Google Scholar]
- Pérez-Pérez, L.; García-Gavín, J.; Piñeiro, B.; Zulaica, A. Biologic-induced urticaria due to polysorbate 80: Usefulness of prick test. Br. J. Dermatol. 2011, 164, 1119–1120. [Google Scholar]
- Ganson, N.J.; Povsic, T.J.; Sullenger, B.A.; Alexander, J.H.; Zelenkofske, S.L.; Sailstad, J.M.; Rusconi, C.P.; Hershfield, M.S. Pre-existing anti-polyethylene glycol antibody linked to first-exposure allergic reactions to pegnivacogin, a PEGylated RNA aptamer. J. Allergy Clin. Immunol. 2016, 137, 1610–1613.e7. [Google Scholar]
- Jo, M.; Ahn, J.Y.; Lee, J.; Lee, S.; Hong, S.W.; Yoo, J.W.; Kang, J.; Dua, P.; Lee, D.K.; Hong, S.; et al. Development of single-stranded DNA aptamers for specific Bisphenol a detection. Oligonucleotides 2011, 21, 85–91. [Google Scholar]
- Niazi, J.H.; Lee, S.J.; Kim, Y.S.; Gu, M.B. ssDNA aptamers that selectively bind oxytetracycline. Bioorg. Med. Chem. 2008, 16, 1254–1261. [Google Scholar]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Li, T.; Yao, F.; An, Y.; Li, X.; Duan, J.; Yang, X.-D. Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo. Molecules 2021, 26, 1067. https://doi.org/10.3390/molecules26041067
Li T, Yao F, An Y, Li X, Duan J, Yang X-D. Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo. Molecules. 2021; 26(4):1067. https://doi.org/10.3390/molecules26041067
Chicago/Turabian StyleLi, Ting, Fengjiao Yao, Yacong An, Xundou Li, Jinhong Duan, and Xian-Da Yang. 2021. "Novel Complex of PD-L1 Aptamer and Holliday Junction Enhances Antitumor Efficacy in Vivo" Molecules 26, no. 4: 1067. https://doi.org/10.3390/molecules26041067