PD-1 disrupted CAR-T cells in the treatment of solid tumors: Promises and challenges

Eileen McGowan; Qimou Lin; Guocai Ma; Haibin Yin; Size Chen; Yiguang Lin

doi:10.1016/j.biopha.2019.109625

PD-1 disrupted CAR-T cells in the treatment of solid tumors: Promises and challenges

Biomed Pharmacother. 2020 Jan:121:109625. doi: 10.1016/j.biopha.2019.109625. Epub 2019 Nov 13.

Authors

Eileen McGowan¹, Qimou Lin², Guocai Ma³, Haibin Yin⁴, Size Chen⁵, Yiguang Lin⁶

Affiliations

¹ Central Laboratory, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China; School of Life Sciences, University of Technology Sydney, Sydney, Australia.
² Department of Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, China.
³ Department of Anesthesiology, Jiangmen Central Hospital, Jiangmen, Guangdong, China.
⁴ Guangzhou Anjie Biomedical Technology Co. Ltd, Guangzhou, China.
⁵ Central Laboratory, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Provincial Engineering Research Center for Esophageal Cancer Precision Treatment, Guangzhou, China.
⁶ Central Laboratory, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China; School of Life Sciences, University of Technology Sydney, Sydney, Australia. Electronic address: Yiguang.Lin@uts.edu.au.

PMID: 31733578
DOI: 10.1016/j.biopha.2019.109625

Abstract

Unprecedented efficacy of chimeric antigen receptor (CAR) T cell therapy in the treatment of hematologic malignancies brings new hope for patients with many cancer types including solid tumors. However, the challenges for CAR-T cell therapy in eradicating solid tumors are immense. To overcome these seemingly intractable hurdles, more "powerful" CAR-T cells with enhanced antitumor efficacy are required. Emerging data support that the anti-tumor activity of CAR-T cells can be enhanced significantly without evident toxicity through simultaneous PD-1 disruption by genome editing. This review focuses on the current progress of PD-1 gene disrupted CAR-T cells in cancer therapy. Here we discuss key rationales for this new combination strategy and summarize the available pre-clinical studies. An update is provided on human clinical studies and available registered cancer clinical trials using CAR-T cells with PD-1 disruption. Future prospects and challenges are also discussed.

Keywords: CAR-T cells; Chimeric antigen receptor T cells; Gene editing; Immunotherapy; PD-1.

Publication types

Review

MeSH terms

Clinical Trials as Topic
Gene Editing
Humans
Immune Checkpoint Inhibitors / therapeutic use*
Immunotherapy, Adoptive*
Neoplasms / therapy*

Substances

Immune Checkpoint Inhibitors