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Adoptive cell transfer therapy for hepatocellular carcinoma

Renyu Zhang, Zhao Zhang, Zekun Liu, Ding Wei, Xiaodong Wu, Huijie Bian, Zhinan Chen

Frontiers of Medicine 2019, Volume 13, Issue 1, Pages 3-11 doi: 10.1007/s11684-019-0684-x

Abstract: The antitumor activities of adoptive cell transfer therapy (ACT), such as strategies based on tumor-infiltrating

Keywords： adoptive cell transfer therapy hepatocellular carcinoma T cell chimeric antigen receptor immunotherapy

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Challenges of NK cell-based immunotherapy in the new era

Fang Fang, Weihua Xiao, Zhigang Tian

Frontiers of Medicine 2018, Volume 12, Issue 4, Pages 440-450 doi: tzg@ustc.edu.cn

Abstract:

Natural killer cells (NKs) have a great potential for cancer immunotherapy because they can rapidly and directly kill transformed cells in the absence of antigen presensitization. Various cellular sources, including peripheral blood mononuclear cells (PBMCs), stem cells, and NK cell lines, have been used for producing NK cells. In particular, NK cells that expanded from allogeneic PBMCs exhibit better efficacy than those that did not. However, considering the safety, activities, and reliability of the cell products, researchers must develop an optimal protocol for producing NK cells from PBMCs in the manufacture setting and clinical therapeutic regimen. In this review, the challenges on NK cell-based therapeutic approaches and clinical outcomes are discussed.

Keywords： natural killer cells immunotherapy adoptive transfer genetic modification immune checkpoint inhibitor

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CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success?

Frontiers of Medicine 2022, Volume 16, Issue 3, Pages 322-338 doi: 10.1007/s11684-021-0901-2

Abstract: Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

Keywords： immunotherapy chimeric antigen receptor solid tumors tumor-associated antigen glycosylation O-glycans adoptive