Promise and Challenges of T Cell Immunotherapy for Osteosarcoma
Abstract
:1. Introduction
2. Immune Checkpoint Inhibitors for Osteosarcoma
3. Adoptive T Cell Immunotherapy for Osteosarcoma
4. Tumor Microenvironment in Osteosarcoma
5. Combination Strategies to Overcome the Limitations of T Cell Immunotherapy against Osteosarcoma
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Clinical Trial | Target | Eligibility (Age) | Phase | Status | Reference |
---|---|---|---|---|---|
Pembrolizumab in patients with advanced sarcomas | PD-1 inhibitor | >12 | phase 2 | completed | NCT02301039 [43,51] |
Nivolumab with or without ipilimumab in treating recurrent or refractory solid tumors or sarcomas | PD-1 inhibitor + CTLA-4 inhibitor | >1 | phase 1 and 2 | active, not recruiting | NCT02304458 [52] |
Nivolumab with or without ipilimumab for patients with metastatic sarcoma | PD-1 inhibitor + CTLA-4 inhibitor | >18 | phase 2 | active, not recruiting | NCT02500797 [46] |
Atezolizumab in pediatric and young adult patients with solid tumors | PD-L1 inhibitor | <30 | phase 1 and 2 | terminated | NCT02541604 [53] |
Durvalumab plus tremelimumab in multiple sarcoma subtypes | PD-L1 inhibitor + CTLA-4 inhibitor | >18 | phase 2 | active, not recruiting | NCT02815995 [47] |
Avelumab in patients with recurrent or progressive osteosarcoma | PD-L1 inhibitor | 12–49 | phase 2 | active, not recruiting | NCT03006848 |
Pembrolizumab in patients with relapsed or metastatic osteosarcoma | PD-1 inhibitor | >18 | phase 2 | terminated | NCT03013127 [44] |
Nivolumab plus ABI-009 (nab-sirolimus) for advanced sarcoma and certain cancers | PD-1 inhibitor | >12 | phase 1 and 2 | completed | NCT03190174 |
Sunitinib and/or nivolumab plus chemotherapy in advanced soft tissue and bone sarcomas | PD-1 inhibitor | 20–80 | phase 1 and 2 | recruiting | NCT03277924 [54] |
Apatinib plus camrelizumab for advanced osteosarcoma | PD-1 inhibitor | phase 2 | completed | NCT03359018 [50] | |
Nivolumab plus ipilimumab in non-resectable sarcoma and endometrial carcinoma | PD-1 inhibitor + CTLA-4 inhibitor | >18 | phase 2 | unknown | NCT03449108 |
Nivolumab and azacitidine for recurrent, resectable osteosarcoma | PD-1 inhibitor | <39 | phase 1 and 2 | recruiting | NCT03628209 |
Socazolimab in high-grade osteosarcoma | PD-L1 inhibitor | 18–55 | phase 1 and 2 | recruiting | NCT03676985 |
Famitinib plus camrelizumab and famitinib alone and famitinib plus ifosfamide in advanced osteosarcoma | PD-1 inhibitor | >12 | phase 1 and 2 | withdrawn | NCT04044378 |
Multi-antigen autoimmune cell injection (MASCT-I)combined with apatinib and/or anti-PD1 antibody in the treatment of tissue sarcoma | PD-1 inhibitor | 14–70 | phase 1 | active, not recruiting | NCT04074564 |
Camrelizumab in combination with neoadjuvant chemotherapy in osteosarcoma | PD-1 inhibitor | 14–65 | phase 2 | recruiting | NCT04294511 |
MAPI + camrelizumab vs. API + apatinib vs. MAPI in patients with a poor response to preoperative chemotherapy for newly diagnosed high-grade osteosarcoma | PD-1 inhibitor | >12 | phase 2 | unknown | NCT04351308 |
Socazolimab for maintenance therapy in patients with high-grade osteosarcoma | PD-L1 inhibitor | >12 | phase 3 | not yet recruiting | NCT04359550 |
Niraparib and dostarlimab in pediatric participants with solid tumors | PD-1 inhibitor | 0.5–17 | phase 1 | recruiting | NCT04544995 |
Oleclumab and durvalumab for the treatment of recurrent, refractory, or metastatic sarcoma | PD-L1 inhibitor | >12 | phase 2 | recruiting | NCT04668300 |
Bempegaldesleukin (BEMPEG: NKTR-214) in combination with nivolumab in recurrent or treatment-resistant cancer | PD-1 inhibitor | <30 | phase 1 and 2 | terminated | NCT04730349 |
Regorafenib and nivolumab in refractory or relapsed osteosarcoma | PD-1 inhibitor | >5 | phase 2 | active, not recruiting | NCT04803877 |
Atezolizumab and cabozantinib for recurrent or metastatic Osteosarcoma | PD-L1 inhibitor | >12 | phase 2 | not yet recruiting | NCT05019703 |
Combination of pembrolizumab and cabozantinib in patients with advanced sarcomas | PD-1 inhibitor | >18 | phase 2 | recruiting | NCT05182164 |
Tislelizumab combined with chemotherapy in bone metastatic sarcoma | PD-1 inhibitor | >18 | phase 2 | recruiting | NCT05241132 |
Neoadjuvant dual checkpoint inhibition and cryoablation in relapsed/refractory pediatric solid tumors | PD-1 inhibitor + CTLA-4 inhibitor | >1 | phase I and 2 | recruiting | NCT05302921 |
Clinical Trial | Target | Eligibility (Age) | Phase | Status | Reference |
---|---|---|---|---|---|
HER2 chimeric antigen receptor expressing T cells in advanced sarcoma | HER2-CAR T cells | Child, adult, older adults | phase 1 | active, not recruiting | NCT00902044 [64] |
Humanized 3F8 bispecific antibody (Hu3F8-BsAb) in relapsed/refractory neuroblastoma, osteosarcoma and other solid tumor cancers | Humanized 3F8 bispecific antibody | 1–17 | phase 1 and 2 | terminated | NCT03860207 |
iC9-GD2-CAR-VZV-CTLs in refractory or metastatic GD2-positive sarcoma and neuroblastoma | GD2 T cells, VZV vaccine, CPM, fludarabine | child, adult, older adult | phase 1 | active, not recruiting | NCT01953900 [92] |
Haploidentical transplant and donor NK cells for solid tumors | Donor NK cell | child, adult, older adult | phase 2 | active, not recruiting | NCT02100891 |
T cells expressing an anti-GD2 CAR in GD2+ solid tumors | GD2-CAR T cell | 1–35 | phase 1 | completed | NCT02107963 |
Activated T cells armed with GD2 bispecific antibody in neuroblastoma and osteosarcoma | GD2 BsAb armed T cell | 1–29 | phase 1 and 2 | unknown | NCT02173093 [91] |
Aβ CD19+ depleted haploidentical transplantation plus zometa for pediatric hematologic malignancies and solid tumors | TCRαβ+/CD19+ depleted haploidentical stem cells | 0.5–21 | phase 1 | recruiting | NCT02508038 |
Treatment of relapsed or refractory neuroblastoma and osteosarcoma with expanded haploidentical NK Cells and Hu14.18-IL2 | Ex vivo expanded and activated haploidentical donor NK cells, and Hu14.18-IL2 | 0.5–26 | phase 1 | withdrawn | NCT03209869 |
Fourth-generation safety-engineered CAR T cells targeting sarcomas | Sarcoma-specific CAR-T cells | 1–75 | phase 1 and 2 | recruiting | NCT03356782 |
Anti-GD2 CAR T cells in high-risk and/or relapsed/refractory neuroblastoma or other GD2-positive solid tumors | GD2-CART 01 | 1–25 | phase 1 and 2 | recruiting | NCT03373097 |
LN-145 or LN-145-S1 in relapsed or refractory cancers | Autologous tumor infiltrating lymphocytes LN-145 or LN-145-S1 | 16–70 | phase 2 | recruiting | NCT03449108 |
NY-ESO-1-specific T cell receptor (TCR) T cell in sarcoma | NY-ESO-1(TCR affinity enhancing T cell | 14–70 | phase 1 | recruiting | NCT03462316 |
EGFR806 CAR T cell immunotherapy for recurrent/refractory solid tumors | EGFR 806CAR(2G)-EGFRt, CD19CAR(2G)-T2A-HER2tG | 1–30 | phase 1 | recruiting | NCT03618381 |
C7R-GD2.CAR T cells for patients with relapsed or refractory neuroblastoma and other GD2-positive cancers | C7R-GD2.CART cells | 1–74 | phase 1 | recruiting | NCT03635632 |
Study of CAR T cells targeting the GD2 with IL-15+i caspase 9 for relapsed/refractory neuroblastoma or relapsed/refractory osteosarcoma | iC9.GD2.CAR.IL-15 T cells | >1.6 | phase 1 | recruiting | NCT03721068 |
Combination immunotherapy targeting sarcomas | Multiple sarcoma-specific CAR-T cells and sarcoma vaccines | 1–75 | phase 1 and 2 | recruiting | NCT04433221 |
B7H3 CAR T cell immunotherapy for recurrent/refractory solid tumors | B7H3-specific CAR, bispecific B7H3xCD19 CAR | <26 | phase 1 | recruiting | NCT04483778 |
GD2-targeted modified T cells (GD2CART) in relapsed/refractory osteosarcoma and neuroblastoma | GD2-CAR T cell | <35 | phase 1 | suspended | NCT04539366 |
Clinical study of CD276 targeted CAR T cell in CD276-positive advanced solid tumor | CD276 CAR T cells | 1–70 | phase 1 | not yet recruiting | NCT04864821 |
B7-H3-CAR T cell therapy for pediatric patients with solid tumors | B7-H3 CAR T cell | <21 | phase 1 | recruiting | NCT04897321 |
HER2 CAR T cells in combination with checkpoint blockade in patients with advanced sarcoma | HER2-CAR T cell + pembrolizumab or nivolumab | 1–25 | Phase 1 | recruiting | NCT04995003 |
Fluorescein-specific (FITC-E2) CAR T cells in combination with folate–fluorescein (UB-TT170) for osteogenic sarcoma | SCRI-E2CAR_EGFRtv1 + UB_TT170 | 15–30 | phase 1 | recruiting | NCT05312411 |
T cell membrane-anchored tumor targeted IL12 (Attil12)-T cell therapy in advanced/metastatic soft tissue and bone sarcoma | autologous tumor-targeted IL12 T cells | >12 | phase 1 | not yet recruiting | NCT05621668 |
CAR.70-engineered IL15-transduced cord blood-derived NK cells in conjunction with lymphodepleting chemotherapy for advanced renal cell carcinoma, mesothelioma and osteosarcoma | CAR.70/IL15-transduced CB-derived NK cells | 18–80 | phase 1 and 2 | not yet recruiting | NCT05703854 |
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Park, J.A.; Cheung, N.-K.V. Promise and Challenges of T Cell Immunotherapy for Osteosarcoma. Int. J. Mol. Sci. 2023, 24, 12520. https://doi.org/10.3390/ijms241512520
Park JA, Cheung N-KV. Promise and Challenges of T Cell Immunotherapy for Osteosarcoma. International Journal of Molecular Sciences. 2023; 24(15):12520. https://doi.org/10.3390/ijms241512520
Chicago/Turabian StylePark, Jeong A, and Nai-Kong V. Cheung. 2023. "Promise and Challenges of T Cell Immunotherapy for Osteosarcoma" International Journal of Molecular Sciences 24, no. 15: 12520. https://doi.org/10.3390/ijms241512520