Maria Pia Morelli, MD, PhD, on Logic-Gated CAR Targeting of Solid Tumors

“We have a product that actually has a logic gate which exploits a specific characteristic of the cancer, loss of heterozygosity. So basically, we screen our patients for their HLA… we know that cancer cells that usually lose their heterozygosity, so [A2 Bio] developed a gated blocker. So basically, you have a CAR-T that with one arm is able to bind the CEA expressed on the cancer cell and triggers the activation of the T-cell in the cancer cell, but at the same time as a blocker that recognizes the HLA expression on the normal cells, so it will prevent those off-cancer, on-target side effects.”

The approved use of cell therapy in oncology is currently limited to indications of chimeric antigen receptor (CAR) T-cell therapy in hematological malignancies, however, many centers and companies are actively working to combat challenges that have prevented its use in solid tumors. One such company is A2 Biotherapeutics, which has developed the A2B530 CAR T-cell therapy with its logic-gated T-cell therapy platform (Tmod) that allows for the selective elimination of CEA-expressing cancer cells that have permanently lost the HLA-A*02 gene. A2B530 is being evaluated in the phase 1 EVEREST-1 clinical trial (NCT05736731).

CGTLive spoke with Maria Pia Morelli, MD, PhD, assistant professor, department of gastrointestinal (GI) medical oncology, division of cancer medicine, MD Anderson Cancer Center, The University of Texas, who serves as a principal investigator in the EVEREST-1 trial. She discussed advantages of A2 Bio’s approach as well as a future program targeting mesothelin.

REFERENCE

A2 Bio announces first patient dosed in phase 1 clinical trial of A2B530, a novel cell therapy for the treatment of colorectal, pancreatic, and non-small cell lung cancers. News release. A2 Biotherapeutics, Inc. May 30, 2023. Accessed June 1, 2023. https://www.a2bio.com/a2-bio-announces-first-patient-dosed-in-phase-1-clinical-trial-of-a2b530-a-novel-cell-therapy-for-the-treatment-of-colorectal-pancreatic-and-non-small-cell-lung-cancers/