The use of cell based immune therapies involving infusion of autologous T-lymphocytes with anti-tumor activity targeting tumor-associated antigens is a rapidly evolving area of research. One approach involves the use of peripheral blood as a source of lymphocytes that are then used in the generation of cytotoxic tumor-specific T cells via introducing a tumor-specific TCR gene into T lymphocytes. NY-ESO-1 is a cancer testis antigen expressed in numerous cancers yet absent in most adult normal tissues apart from high expression in adult testes – thereby making it an ideal target for immunotherapy.
TB1-1301 is a gene-modified T cell product that contains a NY-ESO-1 specific TCR introduced with the MS3II-NY-ESO1-SiTCR retroviral vector. This vector encodes for TCR α and β chains that recognize an NY-ESO-1 derived epitope (amino acids 157-165: SLLMWITQC) that is presented in the context of HLA-A*02:01 and HLA-A*02:06 molecules. The vector also encodes for siRNA (small interfering RNA) that are homologous to the constant region sequence of the endogenous, but not transduced TCR α and β chain mRNAs – these siRNAs in turn increase expression of the transduced TCR. Pre-clinical murine studies demonstrated safety, persistence, and efficacy of transduced T cells. This study represents a Phase 1b study of TBI-1301 in patients with advanced solid tumors, which express NY-ESO-1 (synovial sarcoma, ovarian cancer, and melanoma). A pre-conditioning lymphodepletion regimen of cyclophosphamide 750 mg/m2 will be used on Day -3 and Day -2 prior to infusion of cell product. The objectives of this study include assessing the safety profile of TBI-1301, determining the RP2D dose, and evaluating the efficacy of TBI-1301 via RECIST v1.1.
Clinical trial identification
Legal entity responsible for the study
Tumor Immunotherapy Program, Princess Margaret Cancer Centre.
Takara Bio Inc.
This clinical trial has received funding support from Takara Bio Inc., Japan.
M.O. Butler: Advisory boards: Merck Canada, BMS, Novartis, Immunocore, Immunovaccine, GSK; Research support: Takara Bio Inc. conducting this clinical trial. S. Tanaka: Employee: Takara Bio Inc. N. Hirano: Research support: Takara Bio Inc. All other authors have declared no conflicts of interest.