Personalized peptide vaccination is a promising immunotherapeutic approach in prostate cancer (PCa). We therefore examined whether an approach, utilizing personalized multiple peptide-mediated ex vivo enrichment with effector T cells reactive to multiple tumor-associated antigens (TAAs), could be employed as a basis for the development of T cell immunotherapy of PCa. In this study, we used the non-adherent fraction (lymphocytes) of cryopreserved peripheral blood mononuclear cells from a leukapheretic product of biochemically recurrent (BR, n = 14) and metastatic hormone-refractory (HR, n = 12) PCa patients. The lymphocytes were primed with a pool of mixed overlapping peptides derived from 6 PCa TAAs-PSA, PAP, NY-ESO-1, MAGE-A1, MAGE-A3 and MAGE-A4. After 2 weeks of culture, the cells were stimulated with the peptides and T cell reactivity determined by externalization of CD107a. No TAAs-reactive effector T cells were detected in the patient's lymphocytes after their reconstitution. However, following their priming with the TAAs-derived peptides and 2-week culturing, the lymphocytes became enriched with polyclonal TAAs-reactive effector CD8+ T cells in 8 out of 14 BR and 5 out of 12 HR patients. No such reactive CD8+ T cells were detected in cultured lymphocytes without the peptide priming. Stimulation of the responding cultures with peptides derived from individual TAAs revealed a unique repertoire of the reactive CD8+ T cells. Our strategy revealed that the personalized multiple peptide-mediated ex vivo enrichment with multiple TAAs-reactive T cells in the PCa patient's lymphocytes is a viable approach for development of T cell immunotherapy of PCa.

• Klíčová slova
• CD107a externalization, Personalized T cell immunotherapy, Prostate cancer, Tumor-associated antigens,
• MeSH
• antigeny nádorové imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• imunoterapie metody   MeSH
• individualizovaná medicína metody   MeSH
• kalikreiny imunologie   MeSH
• kultivované buňky MeSH
• leukocyty mononukleární imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanomové antigeny imunologie   MeSH
• membránové proteiny imunologie   MeSH
• nádorové proteiny imunologie   MeSH
• nádory prostaty imunologie   patologie   MeSH
• peptidy imunologie   MeSH
• prostatický specifický antigen imunologie   MeSH
• senioři MeSH
• T-lymfocyty imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• CTAG1B protein, human MeSH Prohlížeč
• kalikreiny MeSH
• KLK3 protein, human MeSH Prohlížeč
• MAGEA1 protein, human MeSH Prohlížeč
• MAGEA3 protein, human MeSH Prohlížeč
• MAGEA4 protein, human MeSH Prohlížeč
• melanomové antigeny MeSH
• membránové proteiny MeSH
• nádorové proteiny MeSH
• peptidy MeSH
• prostatický specifický antigen MeSH