A universal chimeric antigen receptor (CAR)-fragment antibody binder (FAB) split system for cancer immunotherapy.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40614208.
- Also identified by DOI 10.1126/sciadv.adv4937 and PMC identifier 12227065.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Chimeric antigen receptor (CAR) T cell therapy has shown extraordinary results in treating hematological cancer but faces challenges like antigen loss, toxicity, and complex manufacturing. Universal and modular CAR constructs offer improved flexibility, safety, and cost-effectiveness over conventional CAR constructs. We present a CAR-fragment antibody binder (Fab) platform on the basis of an engineered protein G variant (GA1) and Fab scaffolds. Expression of GA1CAR on human CD8<sup>+</sup> T cells leads to antigen recognition and T cell effector function that can be modulated according to the affinity of the CAR for the Fab and of the Fab for the target. GA1CAR T cells can recognize multiple Fab-antigen pairs on breast and ovarian cancer cell lines. Adoptively transferred GA1CAR T cells control tumors in breast cancer xenograft models, and their targeting can be quickly redirected using different Fabs. This versatile "plug-and-play" CAR T platform has potential for application in personalized therapy, preventing antigen loss variant escape, decreasing toxicity, and increasing access.
Medical subject headings
- Receptors, Chimeric Antigen
- Immunoglobulin Fab Fragments
- Immunotherapy, Adoptive
- Immunotherapy
- Neoplasms