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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.
One bottleneck page and 24 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
This paper is the reason TP53 status, MDM2 amplification and CDKN2A loss are read together in tumour genomes. It frames the current drug development around MDM2 inhibitors and mutant p53 reactivators as attempts to restore a network rather than a single protein.
Shares Immunocore, Tebentafusp, TCR-T cell therapy, T-cell engagers (bispecific).
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, Drugging the 'undruggable' cancer targets, The undruggable drivers, TP53.
Shares Immunocore, Tebentafusp, T-cell engagers (bispecific).
Shares Drugging the 'undruggable' cancer targets, The undruggable drivers, TP53, KRAS.
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, The undruggable drivers, TP53, KRAS.
Shares Drugging the 'undruggable' cancer targets, The undruggable drivers, TP53.
Shares Vogelstein, Lane and Levine 2000: surfing the p53 network, The undruggable drivers, TP53, KRAS.
Shares Immatics, Immunocore, TCR-T cell therapy, T-cell engagers (bispecific).