OnCo
ideasIdea

Extending sarcoma TCR-T beyond HLA-A*02

Today's engineered T-cell therapies for sarcoma only work in the ~40-50% of people with one particular HLA type; new receptors for other HLA types would open them to everyone.

Afami-cel and lete-cel require HLA-A*02:01/02:05/02:06. MAGE-A4 and NY-ESO-1 are presented by other alleles (A*24, B*35, C*07); TCR discovery platforms (Immatics, T-knife, Adaptimmune's own) have isolated candidate receptors.

Hypothesis
MAGE-A4- or NY-ESO-1-directed TCR-T restricted to HLA-A*24:02 or HLA-B*35 achieves response rates comparable to afami-cel in synovial sarcoma.
Rationale
Antigen expression is HLA-independent; the binding problem is solved by receptor discovery, not biology.
What would test it
Basket phase 1/2 across HLA types with shared antigen; pooled ORR endpoint.
Maturity
preclinical evidence

Connected

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