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Published on: February 28, 2019
Escape From Synthetic T Cell Activator Tebentafusp by Genomic HLA Loss: A Case Report
Halime Kalkavan1,2,3,4, Andreas Heinold2,5, Siyang Liu1,2
1Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.
HLA
|May 21, 2026
Summary
Resistance to tebentafusp, a treatment for metastatic uveal melanoma, can occur through genomic loss of HLA-A*02:01. This loss prevents antigen presentation, leading to treatment failure and highlighting the need for monitoring resistance mechanisms.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Tebentafusp is a standard treatment for unresectable or metastatic uveal melanoma in patients positive for HLA-A*02:01.
- The mechanisms of resistance to tebentafusp are not yet understood.
Purpose of the Study:
- To investigate the mechanisms of acquired resistance to tebentafusp in a patient with metastatic uveal melanoma.
Main Methods:
- Genomic analysis of a patient's progressive metastasis after 30 months of tebentafusp treatment.
- Assessing the presentation of the target antigen following genomic alterations.
Main Results:
- The patient developed resistance to tebentafusp after 30 months of therapy.
- Genomic loss of the HLA-haplotype carrying HLA-A*02:01 was identified in a progressive metastasis.
- This loss resulted in the failure to present the tebentafusp target antigen.
Conclusions:
- Genomic loss of HLA-A*02:01 is a mechanism of resistance to tebentafusp in uveal melanoma.
- Understanding resistance mechanisms is crucial for monitoring disease and developing new therapeutic strategies for synthetic cancer immunotherapies.
