Experimental Hematology & Oncology · Published 2026-06-18 · DOI 10.1186/s40164-026-00791-3
Tobias Riet, Simon Lennartz, Niklas Bösing, Lars Fabian Prinz, Luise Dähn, Christof Scheid, Michael Hallek, Markus Martin Chmielewski
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.
Abstract from DOAJ. Public domain (CC0 1.0).
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Riet, T., Lennartz, S., Bösing, N., et al. (2026). Overcoming fratricide of CD86 targeting CAR-T cells by defined logic-gate CAR strategy. Experimental Hematology & Oncology. https://doi.org/10.1186/s40164-026-00791-3