Ben Creelan, MD, on the Potential of Logic-gated Tmod CAR-T in Lung Cancer and Other Solid Tumors

This is the second part of an interview with Ben Creelan, MD. For the first part, click here.

“In the case of the A2 Bio approach, they're targeting carcinoembryonic antigen, a marker which showed excellent responses back a decade ago or more, but too much toxicity—too much colitis. By having that logic switch, they're hoping to get rid of the colitis—get rid of the toxicity—and still maintain that tumor potency.”

Efforts to apply targeted cell therapy approaches to the treatment of solid tumors stretch back 10 to 20 years, with early research testing therapies directed against antigens like carcinoembryonic antigen. Although these therapies were effective at destroying cancer cells that express these antigens, they also targeted healthy cells expressing the same antigens. As such, the toxicity of these early targeted cell therapies was too high for them to be clinically feasible. In the proceeding years, cell therapy companies and research institutions have been exploring more complex targeted cell therapy constructs in an attempt to overcome this limitation. One such approach is logic-gated Tmod chimeric antigen receptor T-cell (CAR-T) therapy. Unlike the CAR-T therapies that have been FDA-approved for use against hematological malignancies that simply target and kill cells expressing a known tumor antigen, logic-gated CAR T-cells allow for more selective cell killing. Depending on the particular construct, they are designed to only activate in both the presence of a target antigen and the absence of a different marker expected to only appear on healthy cells (on-off switch construct) or to only activate in the presence of 2 target antigens (on-on switch construct).

CGTLive™ recently spoke to Ben Creelan, MD, a medical oncologist at Moffitt Cancer Center who specializes in the treatment of lung cancer and in oncology cell therapy research, to learn more about novel cell therapy approaches against solid tumors. As part of a larger discussion about different approaches that various companies and institutions are exploring, Creelan gave his opinion on the potential of A2 Biotherapeutics (A2 Bio)’s logic-gated Tmod CAR-T A2B530. He noted that although in-human clinical results are yet to be reported, the preclinical work on A2B530 is promising. He also gave a suggestion on how the base technology could potentially be improved upon in later iterations.

REFERENCE
1. A2 Bio Presents Oral and Poster Presentations Highlighting BASECAMP-1 and EVEREST-1 Patient Screening at 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting. News release. A2 Biotherapeutics, Inc. November 2, 2023. Accessed November 14, 2023. https://www.a2bio.com/a2-bio-presents-oral-and-poster-presentations-highlighting-basecamp-1-and-everest-1-patient-screening-at-2023-society-for-immunotherapy-of-cancer-sitc-annual-meeting/