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Neo-splicetopes, new potential targets in tumor T cell therapy? Pros and Caveats by Christin Beier; Andrian Goede; Peter Kloetzel is a Immunology and Microbiology article available to read on EtoBox.

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sequencing technologies has enabled rapid and comprehensive discovery of cancer mutations in individual patients and provides the opportunity to develop novel approaches, including vaccines, to selectively target neoantigens. A major challenge, however, is that only a small fraction of the mutations generate T cell responses. Currently MHCI binding prediction is used as a major criterion for prioritizing neoantigens. Although this approach enriches for immunogenic neoantigens, a high frequency of false positive remains. For a mutant peptide to be immunogenic, the source protein has to be processed, the resulting mutant peptide needs to bind MHCI, and finally T cells must recognize the MHCI/peptide complex. To investigate the determinants of neoantigen immunogenicity we performed profiling of the immunopeptidome by mass spectrometry. We also assessed the immunogenicity of single amino acid mutations identified in preclinical cancer models by vaccination. We identified novel features of neoantigen immunogenicity that were validated using human data sets. Furthermore we showed that using these determinants improves neoantigen prioritization.

Who reads Neo-splicetopes, new potential targets in tumor T cell therapy? Pros and Caveats?

Author

Christin Beier; Andrian Goede; Peter Kloetzel

Publisher

Elsevier BV

Published

2022

Language

EN

Field

Immunology and Microbiology (Life Sciences)