Bruce Levine, Barbara and Edward Netter Professor in Cancer Gene Therapy at the University of Pennsylvania, shared on X:
“NEW – A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection – link in reply.
- Solid tumors escape TCR-T therapy by losing the restricting HLA allele. What if γδ T cells could carry driver-mutation specificity without giving up their MHC-independent stress sensing?
- The high-affinity, co-receptorm – independent KRAS G12V/HLA-A*11:01 TCR (A11v) was knocked into primary human γδ T cells. They co-express transgenic αβ + endogenous γδ TCRs and lyse KRAS G12V+ tumors in vitro and in vivo
- An mRNA-LNP encoding a secreted mesothelin×CD3 engager (TCE) was dosed to cover HLA-A*11:01 loss. Circulating TCE redirected both γδ A11v and bystander T cells to mesothelin+ targets — and drove higher γδ A11v counts in vivo
- In humanized mice with mixed HLA-A*11:01 +/− KRAS G12V tumors, γδ A11v alone gave transient control; adding LNP-TCE gave complete responses and prolonged survival.”
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