# TCR therapeutics for non-HLA-A*02 patients

Source: https://onco.cc/ideas/idea-prame-tcr-beyond-a02/  
OnCo record `idea-prame-tcr-beyond-a02` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Today's T-cell-receptor drugs only work for people with one tissue type. Building versions for the other common types would roughly double who can be treated.

## Summary

The idea is to build PRAME-directed ImmTAC T-cell engagers for patients who carry HLA-A*24:02 or HLA-A*11:01 rather than HLA-A*02:01, the tissue type that tebentafusp and brenetafusp currently require. The antigen and format stay the same and only the HLA context changes, in principle a solved engineering problem; Immunocore and others already have preclinical ImmTACs against PRAME on HLA-A*24 and A*11, common in East Asian populations. The hypothesis is that these agents match the activity and safety of the A*02 drug, roughly doubling the number of people who could be treated. The test is a phase 1 dose escalation in HLA-A*24:02-positive melanoma in Japan and Korea mirroring IMCgp100-202; the evidence is preclinical and the idea bears on HLA-A*02:01 restriction.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- Hypothesis: PRAME-directed ImmTACs restricted to HLA-A*24:02 or A*11:01 achieve comparable activity and safety to the A*02 agent.
- Rationale: Same antigen, same format; the only variable is the HLA context, which is a solved engineering problem in principle.
- Proposed test: Phase 1 dose escalation in HLA-A*24:02-positive melanoma in Japan and Korea, with ctDNA and OS follow-up mirroring IMCgp100-202.
- Maturity: preclinical-evidence

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- technologies: [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/), [TCR-T cell therapy](https://onco.cc/technologies/tcr-t/)
- targets: [PRAME](https://onco.cc/targets/prame/)
- drugs: [Brenetafusp](https://onco.cc/drugs/brenetafusp/), [Tebentafusp](https://onco.cc/drugs/tebentafusp/)
- terms: [HLA-A*02:01 restriction](https://onco.cc/terms/hla-a02-restriction/)
- key papers: [Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma](https://onco.cc/key-papers/paper-imcgp100-202-n-engl-j-med-2021/), [Tebentafusp: T Cell Redirection for the Treatment of Metastatic Uveal Melanoma](https://onco.cc/key-papers/paper-tebentafusp-melanoma-cancers-basel-2019/), [Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma](https://onco.cc/key-papers/paper-imcgp100-202-n-engl-j-med-2023-update/)

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