Abstract
Even though combining surgery with chemotherapy has significantly improved the prognosis of osteosarcoma patients, advanced, metastatic, or recurrent osteosarcomas are often non-responsive to chemotherapy, making development of novel efficient therapeutic methods an urgent need. Adoptive immunotherapy has the potential to be a useful non-surgical modality for treatment of osteosarcoma. Recently, alternative strategies, including immunotherapies using naturally occurring or genetically modified T cells, have been found to hold promise in the treatment of hematologic malignancies and solid tumors. In this review, we will discuss possible T-cell-based therapies against osteosarcoma with a special emphasis on combination strategies to improve the effectiveness of adoptive T cell transfer and, thus, to provide a rationale for the clinical development of immunotherapies.
Highlights
Osteosarcoma (OS) is an aggressive malignancy of bone thought to originate from mesenchymal stem cells [1]
0701/– 0602/0704 advantages and disadvantages of adoptive γδ T cell transfer immunotherapy are summarized below: [1] it is MHC-independent; [2] it is not affected by immune-escape MHC-downregulation; [3] it is not restricted to any precise sarcoma histotype; [4] it has high rates of ex vivo expansion with simple protocols; [5] it has limited persistence in vivo; and [6] its recognition is limited to extracellular targets [64]
In view of these target antigen candidates, clinical trials with osteosarcoma-specific T cell receptors (TCRs) or chimeric antigen receptor (CAR)-redirected T lymphocytes are planned for the coming years
Summary
Osteosarcoma (OS) is an aggressive malignancy of bone thought to originate from mesenchymal stem cells [1]. Current treatment for newly diagnosed osteosarcoma includes three main components: preoperative chemotherapy, surgical resection, and postoperative chemotherapy [4] This management strategy has improved the outcome of patients with localized osteosarcoma. Robust cancer regressions have been achieved in patients with metastatic melanoma after using T-cell transfer immunotherapy [19] This suggests a possible role and significant efficacy of T cell-mediated treatment of other solid tumors, including osteosarcoma. Results from studies of other solid malignancies, such as melanoma, can point to new immunotherapeutic strategies that may improve survival of patients with advanced osteosarcoma, prevent metastases, and reduce relapse rates in patients with resected tumors. We discuss novel therapeutic strategies for treatment of osteosarcoma, based on our current understanding of the adoptive transfer of unmodified or gene-engineered T cells
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