J Cancer 2020; 11(13):3717-3724. doi:10.7150/jca.39717 This issue

Review

DNT Cell-based Immunotherapy: Progress and Applications

Yingrui Li1,3, Kang Dong2, Xueke Fan4, Jun Xie1, Miao Wang3, Songtao Fu1✉, Qin Li3✉

1. Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, 030000, China.
2. Shanxi Pharmaceutical Group Gene Biotech co. LTD, Taiyuan, 030000, China.
3. Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
4. Department of Gastroenterology, Jincheng People's Hospital, Jincheng, 048000, China.

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Citation:
Li Y, Dong K, Fan X, Xie J, Wang M, Fu S, Li Q. DNT Cell-based Immunotherapy: Progress and Applications. J Cancer 2020; 11(13):3717-3724. doi:10.7150/jca.39717. Available from https://www.jcancer.org/v11p3717.htm

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Abstract

Cancer immunotherapy has firmly established a dominant status in recent years. Adoptive cellular immunotherapy (ACI) is the main branch of immunotherapy. Recently, the immune effector cells of ACI, such as T cells, NK cells, and genetically engineered cells, have been used to achieve significant clinical benefits in the treatment of malignant tumors. However, the clinical applications have limitations, including toxicity, unexpectedly low efficiency, high costs and strict technical requirements. More exploration is needed to optimize ACI for cancer patients. CD3+CD4-CD8- double negative T cells (DNTs) have emerged as functional antitumor effector cells, according to the definition of adoptive immunotherapy. They constitute a kind of T cell subset that mediates nontumor antigen-restricted immunity and has important immune regulatory functions. Preclinical experiments showed that DNTs had a dual effect by killing tumor cells and inhibiting graft-versus-host disease. Notably, DNTs can be acquired from healthy donors and expanded in vitro; thus, allogeneic DNTs may be provided as “off-the-shelf” cellular products that can be readily available for direct clinical application. We review the progress and application of DNTs in immunotherapy. DNTs may provide some novel perspectives on cancer immunotherapy.

Keywords: DNTs, immunotherapy, tumor