Abstract
The clinical benefits of immune checkpoint blockage (ICB) therapy have been widely reported. In patients with cancer, researchers have demonstrated the clinical potential of antitumor cytotoxic T cells that can be reinvigorated or enhanced by ICB. Compared to self-antigens, neoantigens derived from tumor somatic mutations are believed to be ideal immune targets in tumors. Candidate tumor neoantigens can be identified through immunogenomic or immunopeptidomic approaches. Identification of neoantigens has revealed several points of the clinical relevance. For instance, tumor mutation burden (TMB) may be an indicator of immunotherapy. In various cancers, mutation rates accompanying neoantigen loads may be indicative of immunotherapy. Furthermore, mismatch repair-deficient tumors can be eradicated by T cells in ICB treatment. Hence, immunotherapies using vaccines or adoptive T-cell transfer targeting neoantigens are potential innovative strategies. However, significant efforts are required to identify the optimal epitopes. In this review, we summarize the recent progress in the identification of neoantigens and discussed preclinical and clinical studies based on neoantigens. We also discuss the issues remaining to be addressed before clinical applications of these new therapeutic strategies can be materialized.
Highlights
Clinical Significance of Tumor NeoantigensTumor-specific somatic mutation-derived antigens are newly synthesized in tumors and recognized as non-self
(b) mutant proteins resulting from tumor somatic mutations yield mutant peptides, facilitate MHC-I interaction or TCR recognition depending on the mutant position
When patients respond to identified neoantigens, the anti-tumor immune responses are strengthened by these peptide vaccinations
Summary
Tumor-specific somatic mutation-derived antigens (neoantigens) are newly synthesized in tumors and recognized as non-self. (b) mutant proteins resulting from tumor somatic mutations yield mutant peptides, which. (b) mutant proteins resulting from tumor somatic mutations yield mutant peptides, facilitate MHC-I interaction or TCR recognition depending on the mutant position. ICB therapy reinvigorates neoantigen-specific T-cells, supporting their importance in killing tumor cells [10]. Overlapping or indel mutation pe method, tumor tissues are lysed, and peptide/MHC-I complexes are purified by immunoprecipitaquences are analyzed to predict affinity to each MHC-I allele. Mass tumor tissues are lysed, and peptide/MHC-I complexes are purified by immunoprecipitat spectrometry is performed to determine molecular weight and identifying corresponding mutated anti-MHC-I antibodies. T cell responses are investigated by evaluating is performed to determine molecular weight and identifying corresponding mutated pep cytokine production, activation marker expression, and tetramer staining. Researchers have screened patient-derived tumor infiltrating lymphocytes reactivity using a
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