Antibodies that see mutant KRAS and p53 fragments displayed on the cell surface
Cells chop up their internal proteins and display the pieces on their surface. That means even undruggable proteins inside the cell can be attacked from outside by the immune system.
TCR-mimic antibodies and bispecific T-cell engagers can recognise mutant peptide-MHC complexes, including KRAS G12V and TP53 R175H presented on HLA-A*02:01, with published proof of concept. Tebentafusp validated the ImmTAC format clinically in uveal melanoma. The proposal is a coordinated programme covering the commonest driver mutations across the commonest HLA alleles, treating public neoantigens as an off-the-shelf target class.
- The undruggable drivers · The proteins that drive most cancers, such as MYC, mutant p53 and most RAS variants, still have no good drug.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.
Pages like this
not linked directly; found by shared links- TrialIMCgp100-202
Shares Immunocore, Tebentafusp, T-cell engagers (bispecific).
- TargetPRAME
Shares Immatics, Immunocore, TCR-T cell therapy, T-cell engagers (bispecific).
- IdeaTCR therapeutics for non-HLA-A*02 patients
Shares Tebentafusp, TCR-T cell therapy, T-cell engagers (bispecific).
- InstitutionOxford Cancer – Oxford University Hospitals and University of Oxford
Shares Immunocore, Tebentafusp, T-cell engagers (bispecific).
- InstitutionComprehensive Cancer Center Tübingen-Stuttgart
Shares Immatics, Neoantigen, TCR-T cell therapy.
- Targetgp100 (PMEL)
Shares Tebentafusp, TCR-T cell therapy, T-cell engagers (bispecific).
- ProductBrenetafusp
Shares Immunocore, Tebentafusp, T-cell engagers (bispecific).
- IdeaA guaranteed purchase prize for the first drug against a named hard target
Shares TP53, KRAS, The undruggable drivers.