Year: 2026
Type: article
Abstract: Despite its remarkable success in the treatment of several hematological malignancies, cellular immunotherapy using chimeric antigen receptor (CAR) T cells faces significant challenges when treating refractory/relapsed or myeloid malignancies such as AML, CML or multiple myeloma. To overcome the pronounced heterogeneity of such diseases, the search for suitable tumor-associated antigens recently led to surface antigens of the B7 protein family as potential CAR-T cell targets. Using the example of CD86-targeting, we highlight a considerable pitfall of CAR-T therapy which utilizes B7-family proteins as a prominent group of T cell (activation) associated antigens. In a consistent set of in vitro and in vivo experiments we could demonstrate that fratricide among pre-activated CD86-specific CAR-T cells strongly reduces their overall survival and efficacy in tumor killing as recently shown for B7-H3/CD276-targeting CARs. Therefore, we propose a defined combinatorial antigen recognition concept via dual-chain CAR-T cells that incorporate an "AND-gate" mechanism through CD19 primary CAR activation and CD86 conditional co-stimulation to circumvent a severely limited outcome.
Institutions: University of Cologne, University Hospital Cologne
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,290
OpenAlex ID: W7165188314