β-amino acid substitution in the SIINFEKL antigen alters immunological recognition
| Title: | β-amino acid substitution in the SIINFEKL antigen alters immunological recognition |
|---|---|
| Authors: | Ichwaku Rastogi, John A. Mannone, Ruslan Gibadullin, Jena E. Moseman, John Sidney, Alessandro Sette, Douglas G. McNeel, Samuel H. Gellman |
| Source: | Cancer Biology & Therapy, Vol 26, Iss 1 (2025) |
| Publisher Information: | Taylor & Francis Group, 2025. |
| Publication Year: | 2025 |
| Collection: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: | Peptide vaccines, β-amino acid substitutions, proteolysis-resistant peptides, MHC I, CD8 T cells, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: | Background Peptide vaccines offer a direct way to initiate an immunogenic response to a defined antigen epitope. However, peptide vaccines are unstable in vivo, subject to rapid enzymatic proteolysis. Replacement of an α-amino acid residue with a homologous β-amino acid residue (native side chain, but backbone extended by a single CH2 unit) impairs proteolysis at nearby amide bonds. Therefore, antigen analogues containing α-to-β replacements have been examined for functional mimicry of native all-α antigens. Another group previously took this approach in the ovalbumin (OVA) antigen model by evaluating single α-to-β analogues of the murine major histocompatibility complex (MHC) I-restricted peptide SIINFEKL.Methods We re-examined this set of α/β SIINFEKL antigens. We tested the susceptibility to proteolysis in mouse serum and their ability to activate OVA-antigen-specific CD8 T cells in vitro. Additionally, we tested the α/β antigens in vivo for their ability to induce an antigen-specific immunogenic response in naïve mice and in OVA-expressing tumor-bearing mice.Results The α/β antigens were comparable to the native antigen in their susceptibility to proteolysis in serum. Each α/β antigen was capable of activating antigen-specific CD8 T cells in vitro. However, antigen-specific CD8 T cells induced against α/β antigens in vivo were not cross-reactive to the native antigen. Moreover, immunization with α/β analogues did not elicit anti-tumor effects in tumor-bearing mice.Conclusions We conclude that even though α/β analogues of the SIINFEKL antigen can elicit a T cell-based response, this class of backbone-modified peptides is not promising from the perspective of antitumor vaccine development. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 15384047 1555-8576 1538-4047 |
| Relation: | https://doaj.org/toc/1538-4047; https://doaj.org/toc/1555-8576 |
| DOI: | 10.1080/15384047.2025.2486141 |
| Access URL: | https://doaj.org/article/7e1e4cbe2ab142048d142439147f5934 |
| Accession Number: | edsdoj.7e1e4cbe2ab142048d142439147f5934 |
| Database: | Directory of Open Access Journals |
| ISSN: | 15384047 15558576 |
|---|---|
| DOI: | 10.1080/15384047.2025.2486141 |
| Published in: | Cancer Biology & Therapy |
| Language: | English |