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.
- 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: [email protected].
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.