Longevity & AgingPairing a weak glycan-targeting CAR with CD19 revives its cancer-killing power
CD19 CAR T cells treat B cell cancers well but also destroy healthy B cells and can cause serious toxicities. Researchers built a CAR from an IgM antibody (HH2) that recognizes CD75s, a sugar structure capped with α2,6-linked sialic acid that is abundant on lymphoma cells. HH2CAR T cells killed lymphoma cell lines in the dish but released few cytokines, failed against cells with low CD75s density, and could not control lymphoma in mice. Pairing HH2 (signal 1, CD3ζ) with a separate CD19 CAR carrying 4-1BB (signal 2) restored degranulation, avidity, cytokine release, and cell killing, and extended survival in a mantle cell lymphoma mouse model. The combination was also more target-restricted than CD19 alone in cell-line tests. The work is preclinical, but it suggests weak glycan-targeting CARs can be rescued by combinatorial design.
