What is it about?
Tuberculosis (TB) is a disease with a high global burden and for which there is a high unmet need given the limited advances in antibiotic or vaccine development in the last 100 years. Here, we generated a high affinity soluble T cell receptor (TCR) specific for a Mycobacterium tuberculosis (Mtb) peptide presented by the HLA-class I-like molecule HLA-E. Therapeutic targeting HLA-E peptide complexes overcomes HLA-restriction and is therefore applicable to a broad patient population due to HLA-E limited polymorphism. We show that TCR-bispecific molecules, comprised of an affinity-enhanced TCR fused to an anti-CD3 activating domain, specifically induce T cell-mediated killing of Mtb-infected cells. We therefore propose that donor-unrestricted TCR-based immunotherapeutic could be an effective way to target TB infections.
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Photo by National Institute of Allergy and Infectious Diseases on Unsplash
Why is it important?
Our study suggests a novel approach to enhance host T cell immunity against Mtb and provides proof-of-principle for an innovative TCR-based therapeutic strategy overcoming HLA-polymorphism and therefore applicable to a broader patient population.
Perspectives
The years of dedicated work from our team have culminated in novel findings that hold promise for addressing the unmet need in TB treatment. I hope this article makes an impact in the field and provides another approach to target TB infections.
Luis Godinho
Immunocore Ltd
Read the Original
This page is a summary of: An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis, Proceedings of the National Academy of Sciences, May 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2318003121.
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