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Soo Park, MD
Soo Park, MD
Posted: Friday, February 21, 2025
Efforts to understand the immune responses associated with somatic mutations and human polymorphisms of an allogeneic vaccine—known as Vaccimel—have revealed the activation of a broad immune system response against alloantigens, neoantigens, and tumor-associated antigens, according to a study published in Frontiers in Immunology. These findings demonstrate the persistence of immune responses against tumor-specific antigens and tumor-associated antigens, which may explain the overall therapeutic effect of antitumor vaccination, suggested María Marcela Barrio, MD, of Centro de Investigaciones Oncológicas, Buenos Aires, and colleagues.
Paired tumor and germinal samples were obtained from four patients given the vaccine and their vaccine cells. Whole-exome sequencing was performed on these samples to evaluate the immunogens. To predict T-cell epitopes, nonsynonymous coding was employed. Potential epitopes were ranked based on mRNA expression, peptide-HLA stability, and predicted peptide-HLA presentation. Immune responses to these potential epitopes were measured using patients’ peripheral blood mononuclear cells.
Comparisons between patients’ germinal exomes and the vaccine revealed an average of 9,481 coding nonsynonymous variants. In addition, 0.05% to 0.2% of these variants were identified in three of the patients. The fourth patient, who had an increased tumor burden, shared 19.5% of these variants. Furthermore, highly diverse responses against the vaccine peptides were identified in vaccinated patients. An increased number of effector T cells targeting tumor antigens were identified compared with T cells targeting vaccine-exclusive antigens. Moreover, a positive association between the extent of the T-cell response and vaccine antigen expression was identified. However, no evidence of conservation of epitopes across patients was identified.
“Our results have shown that the immunogenicity of off-target antigens did not prevent immune responses against [tumor-associated antigens and tumor-specific antigens], which are the most likely target antigens for therapeutic effect of antitumor vaccination,” concluded the researchers.
Disclosure: The study authors reported no conflicts of interest.
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