Prediction the clinical outcomes of cancer patients after peptide vaccination

• Published in: Journal of clinical oncology Vol. 37; no. 15_suppl; p. e14295
• Main Authors: Toke, Eniko Rita, Megyesi, Mónika, Molnar, Levente, Tóth, József, Lőrincz, Orsolya, van der Burg, Sjoerd H., Welters, Marij, Melief, Cornelis Joseph, Schönharting, Wolfgang, Urban, Sybille, Roehnisch, Tim, Heine, Uwe, Somogyi, Eszter, Csiszovszki, Zsolt, Pántya, Katalin, Páles, Péter, Miklós, István, Lori, Franco, Lisziewicz, Julianna
• Format: Journal Article
• Language: English
• Published: 20.05.2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.15_suppl.e14295

Abstract only e14295 Background: Neoantigen vaccines can activate T-cells that specifically kill tumor cells. However, most vaccine peptides, selected either as HLA-binders or as HLA-presented epitopes, do not induce T-cell responses in HLA allele-matched individuals. We hypothesized that personal-epitopes (PEPIs) binding to multiple autologous HLA-alleles induce potent T-cell responses. Methods: Epitopes binding to single HLA and PEPIs binding to 3 autologous HLA-alleles were identified with our novel and validated PEPI Test (CE Marked) and correlated with CD8+ and CD4+ T-cell responses of (pre)malignant patients vaccinated with Synthetic Long Peptides (SLPs) in 2 clinical trials. A Model Population of 433 HLA-genotyped individuals was used to determine the percentage of subjects with PEPIs from SLPs (PEPI-Score). As a proof of principle, a personal vaccine was developed matching with 14 HLA-alleles of a cancer patient with PEPIs from 12 tumor-antigens. T-cell reactivities were tested by interferon-γ ELISPOT. Results: There was no correlation between single HLA-binding epitopes and HPV-specific T-cell responses of patients. In contrast, there was 90% and 69% agreement between HLA-class-I PEPIs and CD8+ T-cell responses (p < 0.001) and HLA-class-II PEPIs and CD4+ T-cell responses (p = 0.005), respectively. PEPI-Score predicted the T-cell response rate of SLP vaccine clinical trials. As predicted by the PEPI Test, personal vaccine treatment activated tumor-specific T-cells: 91% and 100% of the vaccine peptides elicited CD8+ and CD4+ T-cell responses, respectively. Conclusions: A patient’s HLA genotype is a major determinant of vaccine responses and PEPIs are genetic biomarkers of T-cell responses. PEPI Test prediction of vaccine responses can be utilized by clinicians for selecting the vaccine treatment and for the development of highly immunogenic personal vaccines matched to a patient’s complete HLA genotype (NCT03391232).