An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment

Incorporation of inverted cytokine receptor (ICR) such as interleukin (IL)-4 vs. IL-7 (4/7) ICR is one strategy to improve the antitumor activities of chimeric antigen receptor (CAR) modified T (CAR-T) cells facing immunosuppressive cytokines. Here we report a novel interleukin (IL)-4 vs. IL-21 ICR...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Yi, Jiang, Hua, Luo, Hong, Sun, Yansha, Shi, Bizhi, Sun, Ruixin, Li, Zonghai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Immunology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658891/
https://www.ncbi.nlm.nih.gov/pubmed/31379876
http://dx.doi.org/10.3389/fimmu.2019.01691
_version_ 1783439030260596736
author Wang, Yi
Jiang, Hua
Luo, Hong
Sun, Yansha
Shi, Bizhi
Sun, Ruixin
Li, Zonghai
author_facet Wang, Yi
Jiang, Hua
Luo, Hong
Sun, Yansha
Shi, Bizhi
Sun, Ruixin
Li, Zonghai
author_sort Wang, Yi
collection PubMed
description Incorporation of inverted cytokine receptor (ICR) such as interleukin (IL)-4 vs. IL-7 (4/7) ICR is one strategy to improve the antitumor activities of chimeric antigen receptor (CAR) modified T (CAR-T) cells facing immunosuppressive cytokines. Here we report a novel interleukin (IL)-4 vs. IL-21 ICR (4/21 ICR) that enhanced CAR-T cell potency in IL-4(+) tumor milieu via a different working-mechanism from 4/7 ICR. Upon IL-4 stimulation, 4/21 ICR activated the STAT3 pathway and promoted Th17-like polarization and tumor-targeted cytotoxicity in CAR-T cells in vitro. Furthermore, 4/21 ICR-CAR T cells persisted and eradicated established IL-4(+) tumors in vivo. Thus, 4/21 ICR is a promising clinical CAR-T cell therapeutics for solid tumors rich in IL-4.
format Online
Article
Text
id pubmed-6658891
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-66588912019-08-02 An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment Wang, Yi Jiang, Hua Luo, Hong Sun, Yansha Shi, Bizhi Sun, Ruixin Li, Zonghai Front Immunol Immunology Incorporation of inverted cytokine receptor (ICR) such as interleukin (IL)-4 vs. IL-7 (4/7) ICR is one strategy to improve the antitumor activities of chimeric antigen receptor (CAR) modified T (CAR-T) cells facing immunosuppressive cytokines. Here we report a novel interleukin (IL)-4 vs. IL-21 ICR (4/21 ICR) that enhanced CAR-T cell potency in IL-4(+) tumor milieu via a different working-mechanism from 4/7 ICR. Upon IL-4 stimulation, 4/21 ICR activated the STAT3 pathway and promoted Th17-like polarization and tumor-targeted cytotoxicity in CAR-T cells in vitro. Furthermore, 4/21 ICR-CAR T cells persisted and eradicated established IL-4(+) tumors in vivo. Thus, 4/21 ICR is a promising clinical CAR-T cell therapeutics for solid tumors rich in IL-4. Frontiers Media S.A. 2019-07-19 /pmc/articles/PMC6658891/ /pubmed/31379876 http://dx.doi.org/10.3389/fimmu.2019.01691 Text en Copyright © 2019 Wang, Jiang, Luo, Sun, Shi, Sun and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Yi
Jiang, Hua
Luo, Hong
Sun, Yansha
Shi, Bizhi
Sun, Ruixin
Li, Zonghai
An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment
title An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment
title_full An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment
title_fullStr An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment
title_full_unstemmed An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment
title_short An IL-4/21 Inverted Cytokine Receptor Improving CAR-T Cell Potency in Immunosuppressive Solid-Tumor Microenvironment
title_sort il-4/21 inverted cytokine receptor improving car-t cell potency in immunosuppressive solid-tumor microenvironment
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658891/
https://www.ncbi.nlm.nih.gov/pubmed/31379876
http://dx.doi.org/10.3389/fimmu.2019.01691
work_keys_str_mv AT wangyi anil421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT jianghua anil421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT luohong anil421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT sunyansha anil421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT shibizhi anil421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT sunruixin anil421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT lizonghai anil421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT wangyi il421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT jianghua il421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT luohong il421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT sunyansha il421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT shibizhi il421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT sunruixin il421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment
AT lizonghai il421invertedcytokinereceptorimprovingcartcellpotencyinimmunosuppressivesolidtumormicroenvironment

Ejemplares similares