# Extending sarcoma TCR-T beyond HLA-A*02

Source: https://onco.cc/ideas/idea-tcr-t-beyond-hla-a2/  
OnCo record `idea-tcr-t-beyond-hla-a2` (Idea). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

Afamitresgene autoleucel and letetresgene autoleucel, the engineered T-cell receptor therapies for synovial sarcoma, work only in people whose HLA type is A*02:01, A*02:05 or A*02:06, which excludes around half of patients. This idea would open TCR-T to everyone by discovering receptors that recognise the same antigens, MAGE-A4 and NY-ESO-1, presented by other alleles such as HLA-A*24, HLA-B*35 and HLA-C*07. The rationale is that antigen expression is independent of HLA type, so the barrier is a receptor discovery problem, and platforms at Immatics, T-knife and Adaptimmune have already isolated candidate receptors. The proposed test is a basket phase 1/2 across HLA types; the evidence is preclinical, and the idea addresses the bottleneck of rare and paediatric cancers without markets.

## Fields

- Kind: Idea
- Last checked: 2026-09-07
- 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.
- Proposed test: Basket phase 1/2 across HLA types with shared antigen; pooled ORR endpoint.
- Maturity: preclinical-evidence

## Sources

- ClinicalTrials.gov NCT03967223: IGNYTE-ESO: https://clinicaltrials.gov/study/NCT03967223

## Connected records

- cancers: [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [TCR-T cell therapy](https://onco.cc/technologies/tcr-t/)
- targets: [MAGE-A4](https://onco.cc/targets/mage-a4/)
- drugs: [Afamitresgene autoleucel](https://onco.cc/drugs/afamitresgene-autoleucel/), [Letetresgene autoleucel](https://onco.cc/drugs/letetresgene-autoleucel/)
- key papers: [SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma](https://onco.cc/key-papers/paper-spearhead-1-lancet-2024/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)

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