Will Next-Generation Immunotherapy Overcome the Intrinsic Diversity and Low Immunogenicity of Sarcomas to Improve Clinical Benefit?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Immunogenic Landscape of Sarcomas
3. Immune Checkpoint Inhibitors
3.1. CTLA-4 Blockade
3.2. PD-1/PD-L1 Blockade
3.3. CTLA-4 + PD-1/PD-L1 Immune Checkpoint Inhibitors
4. Adoptive Transfer of Genetically Modified T Cells
4.1. T Cells Engineered to Express TAA-Specific TCRs
4.2. CAR T Cells
5. NK Cell-Based Therapies
6. Bispecific T Cell Engager (BiTE) Antibodies
7. Therapeutic Cancer Vaccines
8. Oncolytic Virus Therapy
9. Future Directions
10. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Trial ID | Phase | Treatment | Sarcoma Type | Status |
---|---|---|---|---|
NCT03074318 | I/II | Avelumab and Trabectedin | Advanced liposarcoma and leiomyosarcoma | Active, not recruiting |
NCT03006848 | II | Avelumab | Recurrent or progressive osteosarcoma | Active, not recruiting |
NCT02834013 | II | Niovlumab and ipilimumab | Advanced angiosarcoma | Recruiting |
NCT03474640 | I | Toripalimab | Advanced soft tissue sarcoma and chondrosarcoma | Recruiting |
NCT04140526 | I | ONC-392 with/without pembrolizumab | Advanced soft tissue sarcoma | Recruiting |
NCT02304458 | I/II | Nivolumab with/without ipilimumab | Recurrent/refractory sarcoma: Ewing sarcoma, osteosarcoma, rhabdomyosarcoma | Active, not recruiting |
NCT04095208 | II | Nivolumab with/without relatlimab | Advanced or metastatic soft tissue sarcoma | Recruiting |
NCT03899805 | II | Eribulin and pembrolizumab | Refractory liposarcoma, leiomyosarcoma, undifferentiated pleomorphic sarcoma | Recruiting |
NCT03141684 | II | Atezolizumab | Advanced alveolar soft part sarcoma | Recruiting |
NCT03338959 | I/II | Pembrolizumab with radiation therapy | Intermediate or high-grade soft tissue sarcoma | Recruiting |
NCT04458922 | II | Atezolizumab | Newly diagnosed/unresectable/metastatic chondrosarcoma, clear cell sarcoma | Recruiting |
NCT03307616 | II | Neoadjuvant nivolumab, nivolumab and ipilimumab, nivolumab and radiation therapy, nivolumab and ipilimumab and radiation therapy | Recurrent or resectable undifferentiated pleomorphic sarcoma or dedifferentiated liposarcoma | Active, not recruiting |
NCT02500797 | II | Nivolumab with/without ipilimumab | Metastatic/unresectable bone sarcoma, liposarcoma, undifferentiated pleomorphic sarcoma | Active, not recruiting |
NCT03463408 | Early I | Neoadjuvant nivolumab and ipilimumab and radiation therapy | Resectable soft tissue sarcoma | Recruiting |
NCT03116529 | I/II | Neoadjuvant durvalumab and tremelimumab and radiation therapy | High risk soft tissue sarcoma | Recruiting |
NCT02815995 | II | Durvalumab and tremelimumab | Advanced/metastatic sarcoma | Active, not recruiting |
NCT03138161 | I/II | Trabectedin and ipilimumab and nivolumab | Advanced/metastatic soft tissue sarcoma | Recruiting |
NCT02992743 | II | Autologous NY-ESO-1 genetically modified T cells (NY-ESO-1c259T) | Advanced myxoid/round cell liposarcoma | Recruiting |
NCT04044768 | II | Autologous ADP-A2M4 genetically modified T cells | Advanced synovial sarcoma or myxoid/ round cell liposarcoma | Recruiting |
NCT03450122 | I | Autologous NY-ESO-1 genetically modified T cells and chemotherapy and aldesleukin with/without immunostimulatory agents: CMB305 and/or antigen-specific vaccine (ID-LV305) | Advanced or recurrent synovial sarcoma, myxoid liposarcoma, NY-ESO-1 positive sarcoma | Recruiting |
NCT02650986 | I/II | Autologous NY-ESO-1 genetically modified T cells with/without decitabine | Advanced/metastatic/unresectable synovial sarcoma | Recruiting |
NCT03250325 | I/II | Autologous NY-ESO-1 genetically modified T cells | Unresectable NY-ESO-1 positive synovial sarcoma | Active, not recruiting |
NCT04556669 | I | Autologous CD22 CAR genetically modified T cells or TILs with scFv fragment of anti-PD-L1 monoclonal antibody | Sarcoma | Recruiting |
NCT03635632 | I | Autologous GD2 CAR genetically modified T cells | Relapsed GD2 positive osteosarcoma, Ewing sarcoma, rhabdomyosarcoma | Recruiting |
NCT03635632 | I/II | Autologous sarcoma specific (CD133, GD2, Muc1, CD117 or other marker) CAR genetically modified T cells | Advanced/ recurrent sarcoma | Recruiting |
NCT03638206 | I/II | Autologous NY-ESO-1 CAR genetically modified T cells | Synovial sarcoma | Recruiting |
NCT00902044 | I | Autologous HER2-CD28 CAR genetically modified T cells | Refractory HER2 positive sarcoma, metastatic HER2 positive osteosarcoma | Active, not recruiting |
NCT04483778 | I | Autologous B7H3 CAR or bispecific B7H3 and CD19 CAR genetically modified T cells | Osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, synovial sarcoma, clear cell sarcoma, soft tissue sarcoma | Recruiting |
NCT04433221 | I/II | Autologous sarcoma specific (GD2, HER2, PSMA, CD276 or other marker) CAR genetically modified T cells | Advanced/recurrent sarcoma | Recruiting |
NCT02100891 | II | HLA-haploidentical haematopoietic cell transplantation and donor NK cell infusion | Advanced/recurrent Ewing sarcoma, rhabdomyosarcoma, osteosarcoma | Active, not recruiting |
NCT02409576 | I/II | Expanded and activated allogenic NK cells | Advanced/metastatic/relapsed Ewing sarcoma, rhabdomyosarcoma | Recruiting |
NCT03860207 | I/II | Humanised 3F8 bispecific antibody (Hu3F8-BsAb) | Relapsed/refractory GD2 positive osteosarcoma | Recruiting |
NCT01803152 | I | Autologous tumour lysate with dendritic cell vaccine with/without myeloid derived suppressor cells inhibition | Relapsed sarcoma | Active, not recruiting |
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Chew, H.Y.; Chan, V.; Simpson, F.; Dolcetti, R. Will Next-Generation Immunotherapy Overcome the Intrinsic Diversity and Low Immunogenicity of Sarcomas to Improve Clinical Benefit? Cancers 2020, 12, 3392. https://doi.org/10.3390/cancers12113392
Chew HY, Chan V, Simpson F, Dolcetti R. Will Next-Generation Immunotherapy Overcome the Intrinsic Diversity and Low Immunogenicity of Sarcomas to Improve Clinical Benefit? Cancers. 2020; 12(11):3392. https://doi.org/10.3390/cancers12113392
Chicago/Turabian StyleChew, Hui Yi, Victor Chan, Fiona Simpson, and Riccardo Dolcetti. 2020. "Will Next-Generation Immunotherapy Overcome the Intrinsic Diversity and Low Immunogenicity of Sarcomas to Improve Clinical Benefit?" Cancers 12, no. 11: 3392. https://doi.org/10.3390/cancers12113392