ASCO 2026 | HLA restrictions shape the potential of TCR-based T-cell engagers
Martin Wermke, MD, TU Dresden University of Technology, Dresden, Germany, comments on the benefits and limitations of bispecific T-cell receptor-based T-cell engagers that targets intracellular antigens presented on the surface by HLA molecules. The novel approach allows for a broader range of targetable antigens compared to traditional bispecifics or CAR-T cell therapies, but notes that this approach is restricted to specific HLA-A alleles, such as HLA-A*02:01. This limitation affects the applicability of these compounds in diverse populations, as the frequency of HLA-A*02:01 varies across different races and ethnicities. This interview took place during the 2026 American Society of Clinical Oncology (ASCO) Meeting in Chicago, IL.
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Transcript
The advantage of this kind of therapy is that it allows you to attack intracellular antigens, which are presented on the surface by means of HLA molecules. So you’re not restricted to surface-only antigens as the classic bispecifics or CAR-T cell approaches are. The downside of that is that these kind of approaches only work in the context of a given HLA-A allele, so most of the compounds developed thus far focus on HLA-A0201, which is present in 40 to 50 percent of the western population, so the most frequent one...
The advantage of this kind of therapy is that it allows you to attack intracellular antigens, which are presented on the surface by means of HLA molecules. So you’re not restricted to surface-only antigens as the classic bispecifics or CAR-T cell approaches are. The downside of that is that these kind of approaches only work in the context of a given HLA-A allele, so most of the compounds developed thus far focus on HLA-A0201, which is present in 40 to 50 percent of the western population, so the most frequent one. It is less frequent in other races and ethnicities.
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