Cargando…
Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models
Adoptive chimeric antigen receptor-modified T or NK cells (CAR-T or CAR-NK) offer new options for cancer treatment. CAR-T therapy has achieved encouraging breakthroughs in the treatment of hematological malignancies. However, their therapeutic efficacy against solid tumors is limited. New regimens,...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205314/ https://www.ncbi.nlm.nih.gov/pubmed/30410941 http://dx.doi.org/10.1155/2018/4263520 |
_version_ | 1783366171826847744 |
---|---|
author | Zhang, Qing Zhang, Haixu Ding, Jiage Liu, Hongyan Li, Huizhong Li, Hailong Lu, Mengmeng Miao, Yangna Li, Liantao Zheng, Junnian |
author_facet | Zhang, Qing Zhang, Haixu Ding, Jiage Liu, Hongyan Li, Huizhong Li, Hailong Lu, Mengmeng Miao, Yangna Li, Liantao Zheng, Junnian |
author_sort | Zhang, Qing |
collection | PubMed |
description | Adoptive chimeric antigen receptor-modified T or NK cells (CAR-T or CAR-NK) offer new options for cancer treatment. CAR-T therapy has achieved encouraging breakthroughs in the treatment of hematological malignancies. However, their therapeutic efficacy against solid tumors is limited. New regimens, including combinations with chemical drugs, need to be studied to enhance the therapeutic efficacy of CAR-T or NK cells for solid tumors. An epithelial cell adhesion molecule- (EpCAM-) specific second-generation CAR was constructed and transduced into NK-92 cells by lentiviral vectors. Immune effects, including cytokine release and cytotoxicity of the CAR-NK-92 cells against EpCAM-positive colon cancer cells, were evaluated in vitro. Synergistic effects of regorafenib and CAR-NK-92 cells were analyzed in a mouse model with human colorectal cancer xenografts. The CAR-NK-92 cells can specifically recognize EpCAM-positive colorectal cancer cells and release cytokines, including IFN-γ, perforin, and granzyme B, and show specific cytotoxicity in vitro. The growth suppression efficacy of combination therapy with regorafenib and CAR-NK-92 cells on established EpCAM-positive tumor xenografts was more significant than that of monotherapy with CAR-NK-92 cells or regorafenib. Our results provided a novel strategy to treat colorectal cancer and enhance the therapeutic efficacy of CAR-modified immune effector cells for solid tumors. |
format | Online Article Text |
id | pubmed-6205314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-62053142018-11-08 Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models Zhang, Qing Zhang, Haixu Ding, Jiage Liu, Hongyan Li, Huizhong Li, Hailong Lu, Mengmeng Miao, Yangna Li, Liantao Zheng, Junnian J Immunol Res Research Article Adoptive chimeric antigen receptor-modified T or NK cells (CAR-T or CAR-NK) offer new options for cancer treatment. CAR-T therapy has achieved encouraging breakthroughs in the treatment of hematological malignancies. However, their therapeutic efficacy against solid tumors is limited. New regimens, including combinations with chemical drugs, need to be studied to enhance the therapeutic efficacy of CAR-T or NK cells for solid tumors. An epithelial cell adhesion molecule- (EpCAM-) specific second-generation CAR was constructed and transduced into NK-92 cells by lentiviral vectors. Immune effects, including cytokine release and cytotoxicity of the CAR-NK-92 cells against EpCAM-positive colon cancer cells, were evaluated in vitro. Synergistic effects of regorafenib and CAR-NK-92 cells were analyzed in a mouse model with human colorectal cancer xenografts. The CAR-NK-92 cells can specifically recognize EpCAM-positive colorectal cancer cells and release cytokines, including IFN-γ, perforin, and granzyme B, and show specific cytotoxicity in vitro. The growth suppression efficacy of combination therapy with regorafenib and CAR-NK-92 cells on established EpCAM-positive tumor xenografts was more significant than that of monotherapy with CAR-NK-92 cells or regorafenib. Our results provided a novel strategy to treat colorectal cancer and enhance the therapeutic efficacy of CAR-modified immune effector cells for solid tumors. Hindawi 2018-10-15 /pmc/articles/PMC6205314/ /pubmed/30410941 http://dx.doi.org/10.1155/2018/4263520 Text en Copyright © 2018 Qing Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhang, Qing Zhang, Haixu Ding, Jiage Liu, Hongyan Li, Huizhong Li, Hailong Lu, Mengmeng Miao, Yangna Li, Liantao Zheng, Junnian Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models |
title | Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models |
title_full | Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models |
title_fullStr | Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models |
title_full_unstemmed | Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models |
title_short | Combination Therapy with EpCAM-CAR-NK-92 Cells and Regorafenib against Human Colorectal Cancer Models |
title_sort | combination therapy with epcam-car-nk-92 cells and regorafenib against human colorectal cancer models |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205314/ https://www.ncbi.nlm.nih.gov/pubmed/30410941 http://dx.doi.org/10.1155/2018/4263520 |
work_keys_str_mv | AT zhangqing combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT zhanghaixu combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT dingjiage combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT liuhongyan combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT lihuizhong combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT lihailong combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT lumengmeng combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT miaoyangna combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT liliantao combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels AT zhengjunnian combinationtherapywithepcamcarnk92cellsandregorafenibagainsthumancolorectalcancermodels |