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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

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373693" target="_blank" >RIV/00216208:11130/17:10373693 - isvavai.cz</a>

  • Nalezeny alternativní kódy

    RIV/00064203:_____/17:10373693

  • Výsledek na webu

    <a href="https://doi.org/10.1007/s12032-017-1035-x" target="_blank" >https://doi.org/10.1007/s12032-017-1035-x</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1007/s12032-017-1035-x" target="_blank" >10.1007/s12032-017-1035-x</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Personalized ex vivo multiple peptide enrichment and detection of T cells reactive to multiple tumor-associated antigens in prostate cancer patients

  • Popis výsledku v původním jazyce

    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 TAAsPSA, 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&apos;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&apos;s lymphocytes is a viable approach for development of T cell immunotherapy of PCa.

  • Název v anglickém jazyce

    Personalized ex vivo multiple peptide enrichment and detection of T cells reactive to multiple tumor-associated antigens in prostate cancer patients

  • Popis výsledku anglicky

    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 TAAsPSA, 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&apos;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&apos;s lymphocytes is a viable approach for development of T cell immunotherapy of PCa.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    30102 - Immunology

Návaznosti výsledku

  • Projekt

    <a href="/cs/project/NV16-28135A" target="_blank" >NV16-28135A: Příprava polyklonálních nádorově specifických T-buněk pro adoptivní buněčnou imunoterapii karcinomu prostaty</a><br>

  • Návaznosti

    S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Ostatní

  • Rok uplatnění

    2017

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    Medical Oncology

  • ISSN

    1357-0560

  • e-ISSN

  • Svazek periodika

    34

  • Číslo periodika v rámci svazku

    10

  • Stát vydavatele periodika

    US - Spojené státy americké

  • Počet stran výsledku

    13

  • Strana od-do

  • Kód UT WoS článku

    000411872900008

  • EID výsledku v databázi Scopus

    2-s2.0-85028701567