Current Perspectives on Emerging CAR-Treg Cell Therapy: Based on Treg Cell Therapy in Clinical Trials and the Recent Approval of CAR-T Cell Therapy

Koeun Kang; Junho Chung; Jaeseok Yang; Hyori Kim

doi:10.4285/jkstn.2017.31.4.157

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Kang, Chung, Yang, and Kim: Current Perspectives on Emerging CAR-Treg Cell Therapy: Based on Treg Cell Therapy in Clinical Trials and the Recent Approval of CAR-T Cell Therapy

Review Article

The Journal of the Korean Society for Transplantation 2017; 31(4): 157-169.

Published online: 31 December 2017

DOI: https://doi.org/10.4285/jkstn.2017.31.4.157

Current Perspectives on Emerging CAR-Treg Cell Therapy: Based on Treg Cell Therapy in Clinical Trials and the Recent Approval of CAR-T Cell Therapy

Koeun Kang¹, Junho Chung, M.D.¹, Jaeseok Yang, M.D.^2,³, Hyori Kim, Ph.D.⁴

¹Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.

²Transplantation Center, Seoul National University Hospital, Seoul, Korea.

³Department of Surgery, Seoul National University Hospital, Seoul, Korea.

⁴Biomedical Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.

Corresponding author: Hyori Kim. Asan Institute for Life Sciences, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea. Tel: 82-2-3010-5825, Fax: 82-2-3010-4182, hyorikim@amc.seoul.kr

Received 26 October 2017 Accepted 30 October 2017

Rhe Korean Society for Transplantation

Abstract

Regulatory T cells (Treg) naturally rein in immune attacks, and they can inhibit rejection of transplanted organs and even reverse the progression of autoimmune diseases in mice. The initial safety trials of Treg against graft-versus-host disease (GVHD) provided evidence that the adoptive transfer of Treg is safe and capable of limiting disease progression. Supported by such evidence, numerous clinical trials have been actively investigating the efficacy of Treg targeting autoimmune diseases, type I diabetes, and organ transplant rejection, including kidney and liver. The limited quantity of Treg cells harvested from peripheral blood and subsequent in vitro culture have posed a great challenge to large-scale clinical application of Treg; nevertheless, the concept of CAR (chimeric antigen receptor)-Treg has emerged as a potential resolution to the problem. Recently, two CAR-T therapies, tisagenlecleucel and axicabtagene ciloleucel, were approved by the US FDA for the treatment of refractory or recurrent acute lymhoblastic leukemia. This approval could serve as a guideline for the production protocols for other genetically engineered T cells for clinical use as well. The phase I and II clinical trials of these agents has demonstrated that genetically engineered and antigen-targeting T cells are safe and efficacious in humans. In conclusion, both the promising results of Treg cell therapy from the clinical studies and the recent FDA approval of CAR-T therapies are paving the way for CAR-Treg therapy in clinical use.

Keywords: Transplantation, Rejection, Autoimmune disease, Regulatory T cells, Chimeric antigen receptor

Figures and Tables

Table 1

Quality assurance of tisagenlecleucel

Abbreviations: CAR, chimeric antigen receptor; IFN, interferon; qPCR, quantitative polymerase chain reaction; VSV-G, vesicular stomatitis virus-G.

ACKNOWLEDGEMENT

This research was supported by a grant (17172바의안212) from Ministry of Food and Drug Safety in 2017. This study was supported by the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (NRF-2015M3A9D3051413, NRF-2017M3A9G5057229).

Notes

^{CONFLICT OF INTEREST} The authors declare no conflict of interest.

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