Abstract SY13-03: Allogeneic CAR T: Science at scale

Abstract Chimeric antigen receptor (CAR) T-cell therapy offers curative potential. A major goal has been translating this promise into an off-the-shelf platform that can be manufactured at scale and delivered without complex logistics. Allogeneic CAR T represents the leading strategy to broaden access and standardize treatment.This presentation reviews scientific advances and translational evidence that have moved allogeneic CAR T from concept to clinical feasibility. Advances in gene editing have enables key progress by overcoming fundamental immunologic barriers. Disruption of the endogenous T-cell receptor substantially mitigates graft-versus-host disease risk. Protecting allogeneic CAR T cells from host allo-rejection remains more challenging. Early clinical data demonstrated that transient host immune suppression with a T-cell-directed antibody can support CAR T cell engraftment and antitumor activity. Newer strategies, including CD70-based Dagger Technology, enable allogeneic CAR T cells to selectively deplete recipient immune populations involved in rejection and have produced more robust expansion and persistence. Additional approaches to reduce immune recognition of HLA-mismatched donor-derived CAR T cells are also emerging.As the field matures, success will depend on pairing allogeneic CAR T platforms with the right disease settings and enabling industrial-scale manufacturing. In hematologic malignancies, ctDNA-guided strategies may enable earlier deployment of allogeneic CAR T cells to prevent disease recurrence. Cemacabtagene ansegedleucel (cema-cel) in the ALPHA3 trial is advancing as a potential registrational study in LBCL designed to test this approach. In solid tumors, CAR T therapy, including the allogeneic product ALLO-316, has shown deep, durable responses. Beyond oncology, CAR T is being explored in autoimmune disease to deplete pathogenic B cells and reset the immune system, potentially enabling durable remissions. Together, these advances position allogeneic CAR T therapy as a scalable, accessible therapeutic class approaching the manufacturing efficiency and cost structure of biologics. Citation Format: David D. Chang. Allogeneic CAR T: Science at scale [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr SY13-03.