Dr Srour on the Utility of CTX130 in 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 utility of the allogeneic CAR T-cell therapy CTX130 as well as unmet needs within the advanced clear cell renal cell carcinoma patient population, highlighting the phase 1 COBALT-RCC trial (NCT04438083), which is aiming to address these needs.

Notably, updated findings from the COBALT-RCC study were shared at the 2024 AACR Annual Meeting. CTX130 is an allogeneic CAR T-cell therapy, akin to other commercially available CAR T-cell products approved for patients with hematologic malignancies, Srour begins. Like typical CAR T-cell therapies, CTX130 uses a chimeric antigen receptor construct aimed at a specific target—in this case, CD70, he reports. What sets CTX130 apart is its status as a generic off-the-shelf product, Srour explains.

To enhance the efficacy of CTX130, investigators incorporated T-cell receptor (TCR) knockout to prevent certain diseases and beta-2 microglobulin knockout to facilitate engraftment without host rejection, he elucidates. Thus, CTX130 encompasses these 3 genetic modifications: CD70 CAR T-cell incorporation, CD70 knockout to prevent cells from killing the CAR T-cell product, and TCR and beta-2 microglobulin knockouts for enhanced engraftment, Srour expands.

Furthermore, in the realm of solid tumors, challenges remain in rendering CAR T-cell therapy effective, he continues, saying that among these hurdles is identifying the optimal target amidst the myriad targets within tumor cells, a task requiring extensive study and research. Additionally, overcoming the suppressive solid tumor microenvironment presents a significant challenge that is distinct from challenges seen with CAR T-cell therapy in liquid tumors, Srour says. Despite these obstacles, progress has been made in recent years toward overcoming these challenges and achieving success in solid tumor therapy, according to Srour. Investigators anticipate continued advancements in the near future, with the hope of replicating the success with CAR T-cell therapy observed in hematologic malignancies, he concludes.