Abstract 3556: Immunopeptidomics-guided tumor antigen warehouse design and first clinical application of a personalized peptide vaccine for prostate cancer
2022-06-15

Abstract Prostate cancer is the second most common malignancy in men with radical prostatectomy and radio-therapy being the primary curative treatment modalities in localized disease. However, up to 30% of patients experience recurrence that frequently leads to the development of metastatic disease associated with poor outcome. Therefore, novel, effective and low-side effect treatment options are essential, in particular for elderly and frail prostate cancer patients not eligible for intense therapy. Whereas, immune checkpoint inhibitors showed limited efficacy in prostate cancer so far, targeted T cell-based approaches with bispecific antibodies and cancer vaccines achieved promising results in this tumor entity. In this study, we established a prostate-associated off-the-shelf peptide warehouse, using mass-spectrometry-based immunopeptidome analysis of a large cohort of primary prostate tissue (n = 51), for the development of a broadly applicable personalized vaccine. The prostate dataset (23 prostate cancer, 12 adjacent benign, 16 benign prostate samples) comprising 29,893 HLA class I and II molecules, was compared to the immunopeptidomes of various benign non-prostate tissues (HLA-Ligand Atlas) to identify prostate exclusive antigens. Further antigen selection was based on the high presentation frequency. In total, 30 frequently expressed and prostate exclusive HLA class I peptides restricted to the six common allotypes HLA-A*02, -A*03, -A*24, -B*07, -B*08 and -B*40, covering more than 76% of the world population for at least one allotype, and five promiscuous HLA-DR restricted peptides found in up to 37% of prostates were selected. Immunogenicity was validated by IFNγ ELISPOT screening for preexisting T cell responses, as well as by in vitro priming experiments of naïve T cells in prostate cancer patients and healthy volunteers. The peptide warehouse will enable the formulation of personalized vaccines based on individual HLA allotype and immunopeptidome analysis of patient’s tumor samples in a reasonable time and cost frame within large cohort studies. We provided first evidence for the feasibility of this approach by designing a personalized immunopeptidome-guided peptide vaccine for a patient with metastatic prostate cancer. The vaccine was adjuvanted with the toll-like receptor 1/2 agonist XS15 emulsified in Montanide࣪ ISA51 VG and applied three times within a 12-week interval. Induction of a profound T cell response targeting 7/9 (78%) vaccine peptides was observed one week after the second vaccination. T cell responses have been persisting for almost two years in the patient, and in combination with androgen deprivation therapy enabled persistent PSA remission. In conclusion, we designed an immunopeptidomics-guided peptide warehouse and provided first evidence for its personalized application in prostate cancer patients. Citation Format: Yacine Maringer, Lena Freudenmann, Annika Nelde, Jonas S. Heitmann, Helmut R. Salih, Marissa Dubbelaar, Jörg Hennenlotter, Arnulf Stenzl, Jens Bedke, Hans-Georg Rammensee, Juliane S. Walz. Immunopeptidomics-guided tumor antigen warehouse design and first clinical application of a personalized peptide vaccine for prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3556.