Potential of human γδ T cells for immunotherapy of osteosarcoma

Recurrent or metastatic osteosarcomas remain a challenging malignancy to treat. Therefore, development and testing of novel therapeutic strategies to target these patients are needed. Adoptive cellular therapy strategies are being evaluated intensively as a novel therapeutic strategy for cancer. Unlike alpha beta T cells requiring antigen processing and MHC-restricted peptide displayed by antigen-presenting cells, gamma delta T cells exhibit the potent MHC-unrestricted lytic activity against various tumors in vitro and in vivo. The recent considerable success of gamma delta T cell-based immunotherapy in lung metastasis of renal cell carcinoma warrants further efforts to apply this treatment to other cancers including osteosarcoma, especially recurrent and metastatic osteosarcomas. In this review, we summarize the available evidence on gamma delta T cell-based immunotherapy for osteosarcoma that has been achieved to date. More importantly, we discuss potential strategies of the combination of expanded gamma delta T cells and bisphosphonates, and modification and expansion of alpha beta TCR modified gamma delta T cells for improving its efficacy for the treatment of osteosarcoma.