Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F17%3A10360684" target="_blank" >RIV/00216208:11110/17:10360684 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/17:10360684 RIV/00064203:_____/17:10360684

Výsledek na webu

<a href="http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171539" target="_blank" >http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171539</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1371/journal.pone.0171539" target="_blank" >10.1371/journal.pone.0171539</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy

Popis výsledku v původním jazyce

High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h. Moreover, DC-based HHP lung cancer vaccine showed functional plasticity after transfer into serum-containing media and stimulation with LPS or CD40L after additional 24h. LPS and CD40L stimulation further differentially enhanced the expression of costimulatory molecules and production of IL-12p70. DC-based HHP lung cancer vaccine decreased the number of CD4(+) CD25(+) Foxp3(+) T regulatory cells and stimulated IFN-gamma-producing tumor antigenspecific CD4(+) and CD8(+) T cells from non-small cell lung cancer (NSCLC) patients. Tumor antigen specific CD8(+) and CD4(+) T cell responses were detected in NSCLC patient&apos;s against a selected tumor antigens expressed by lung cancer cell lines used for the vaccine generation. We also showed for the first time that protein antigen from HHP-killed lung cancer cells is processed and presented by DC to CD8(+) T cells. Our results represent important preclinical data for ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa) in combination with chemotherapy and immune enhancers.

Název v anglickém jazyce

Generation of dendritic cell-based vaccine using high hydrostatic pressure for non-small cell lung cancer immunotherapy

Popis výsledku anglicky

High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h. Moreover, DC-based HHP lung cancer vaccine showed functional plasticity after transfer into serum-containing media and stimulation with LPS or CD40L after additional 24h. LPS and CD40L stimulation further differentially enhanced the expression of costimulatory molecules and production of IL-12p70. DC-based HHP lung cancer vaccine decreased the number of CD4(+) CD25(+) Foxp3(+) T regulatory cells and stimulated IFN-gamma-producing tumor antigenspecific CD4(+) and CD8(+) T cells from non-small cell lung cancer (NSCLC) patients. Tumor antigen specific CD8(+) and CD4(+) T cell responses were detected in NSCLC patient&apos;s against a selected tumor antigens expressed by lung cancer cell lines used for the vaccine generation. We also showed for the first time that protein antigen from HHP-killed lung cancer cells is processed and presented by DC to CD8(+) T cells. Our results represent important preclinical data for ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa) in combination with chemotherapy and immune enhancers.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30102 - Immunology

Projekt

—

Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

PLoS One

ISSN

1932-6203

e-ISSN

—

Svazek periodika

12

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

—

Kód UT WoS článku

000394244300028

EID výsledku v databázi Scopus

2-s2.0-85012123599