Current status of engineered T-cell therapy for synovial sarcoma

Abstract

Synovial sarcoma is a rare soft tissue sarcoma characterized by a t(X;18) translocation, which results in a SYT-SSX gene fusion. In the metastatic setting, chemotherapy has limited, durable efficacy prompting the necessity for new therapeutic modalities. One emerging new strategy involves T-cell-directed therapy such as tumor-infiltrating lymphocytes or the development of T cells that are genetically engineered to express a T-cell receptor against a cancer testis antigen. Of these approaches, engineered T cells that recognize NY-ESO-1 are the furthest along in development. Completed and on-going clinical trials have shown promise and there are efforts to continue to optimize the current approach.

Keywords: NY-ESO-1; adoptive T-cell therapy; chimeric antigen receptor; engineered T cell; synovial sarcoma; tumor-infiltrating lymphocytes.

Figure 1.. Adoptive cell therapy approaches.

Treatment with tumor-infiltrating lymphocytes (TILs) involves harvesting of T cells from tumor tissue, isolation of TILs, expansion with IL-2 and then infusion of TILs back into the patient. Isolation of TILs active against tumor cells can be done prior to infusion back into patients through co-culture assays. T cells can also be harvested through apheresis and genetically modified ex vivo to express T-cell receptors (TCRs). TCRs require MHC complexes for anti-tumor activity. Patients are given lympho-depletion chemotherapy prior to infusion of engineered T cells. Adapted from [41].