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Personalized ex vivo multiple peptide enrichment and detection of T cells reactive to multiple tumor-associated antigens in prostate cancer patients
P. Taborska, D. Stakheev, Z. Strizova, K. Vavrova, M. Podrazil, J. Bartunkova, D. Smrz,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články
Grantová podpora
NV16-28135A
MZ0
CEP - Centrální evidence projektů
Digitální knihovna NLK
Plný text - Článek
NLK
ProQuest Central
od 1997-03-01 do Před 1 rokem
Medline Complete (EBSCOhost)
od 2013-03-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 1997-03-01 do Před 1 rokem
- 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
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.
Citace poskytuje Crossref.org
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- $a 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.
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