The CD19 CAR T hinge region influences avidity and cytotoxicity in CD19 SNP variants in B-cell Lymphoma
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Outcomes after CD19 CAR T-cell therapy in patients with diffuse large B-cell lymphoma are variable, partly influenced by the germline CD19 SNP rs2904880 (V174/L174). Using structural modeling, lymphoma cell lines, and patient data, we demonstrate that CAR hinge choice (CD8 versus CD28) differentially modulates avidity and cytotoxicity against CD19 V174 and V174L variants and correlates with distinct clinical responses to axi-cel and tisa-cel. This suggests that CD19 genotyping may guide CAR T selection.
