ArticleFrontiers in immunology2026
Peptide optimization to improve antigen presentation and antitumor responses in sarcoma.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
Sarcomas are rare and heterogeneous malignancies for which therapeutic options remain limited, particularly in advanced disease. Standard treatments, including surgery, radiotherapy, chemotherapy, and approved targeted agents, provide marginal improvements in progression-free and overall survival, highlighting the need for immunotherapeutic strategies. Therapeutic cancer vaccines represent a promising strategy, but clinical efficacy has been limited by low antigen immunogenicity and an immunosuppressive tumor microenvironment (TME). Enhancing antigen presentation and T-cell receptor (TCR) engagement through heteroclitic peptide engineering may overcome immune tolerance and improve vaccine efficacy. Preliminary data from our group demonstrate that heteroclitic peptides modified at TCR-facing and anchor residues enhance antigen-specific T-cell recognition, cross-reactivity with wild-type epitopes, and tumor control in preclinical models. In this study, we aim to design and validate optimized heteroclitic epitopes derived from sarcoma-associated TAAs. We developed an integrated computational and experimental workflow to identify and optimize HLA-A*02:01-restricted epitopes derived from sarcoma-associated TAAs. Candidate wild-type (WT) peptides were selected using NetMHCpan 4.1 based on predicted HLA binding affinity and subsequently engineered through systematic amino acid substitutions to generate heteroclitic variants. Optimized peptides were evaluated by structural modeling and molecular docking, followed by experimental
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