Dr Srour on the Ongoing Investigation of CAR T-Cell Therapy in Advanced RCC

Samer A. Srour, MB ChB, MS, assistant professor, Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the investigation of the allogeneic CAR T-cell therapy CTX131 in patients with advanced clear cell renal cell carcinoma (ccRCC).

Updated findings from the phase 1 COBALT-RCC trial (NCT04438083), which evaluated CTX130 in patients with advanced ccRCC, were shared at the 2024 AACR Annual Meeting. Notably, CTX130 is an allogeneic CAR T-cell therapy similiar to other commercially available CAR T-cell therapies approved for patients with hematologic malignancies. These outcomes left investigators feeling optimistic, yet as researchers, Srour states that he and colleagues perpetually seek avenues for improvement, posing a critical question: Could outcomes be enhanced beyond current achievements, such as bolstering disease control rates above 80%? Consequently, investigators embarked on a quest to identify potential genetic modifications for CAR T-cell therapy that could elevate efficacy levels. Although patient enrollment and treatment with CTX130 were ongoing, parallel efforts were underway to refine the therapy, Srour reports.

Through experimentation, investigators identified 2 promising modifications that showed considerable promise in enhancing the potency and longevity of CAR T-cells, thereby amplifying their persistence within the body, Srour expands. Additionally, targeting the TGFβreceptor proved instrumental in overcoming the suppressive nature of the tumor microenvironment, according to Srour. By eliminating this barrier, CAR T-cells were empowered to better infiltrate and combat tumors, Srour says. These advancements culminated in the development of CTX131, the next iteration of CDX130, which embodies these critical genetic enhancements, he elucidates.

Presently, the investigation of CTX131 is underway at The University of Texas MD Anderson Cancer Center and other institutions, Srour continues. Although still in its early stages, investigators have commenced treatment on a select cohort of patients. Investigators anticipate accumulating valuable insights and data that will further elucidate the potential of CTX131, Srour concludes.