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Review
. 2017 Aug 4;8(38):64607-64621.
doi: 10.18632/oncotarget.19929. eCollection 2017 Sep 8.

CAR-T cell therapy in ovarian cancer: from the bench to the bedside

Xinxin Zhu  1   2 , Han Cai  1 , Ling Zhao  1 , Li Ning  1 , Jinghe Lang  1
Affiliations
Review

CAR-T cell therapy in ovarian cancer: from the bench to the bedside

Xinxin Zhu et al. Oncotarget. .

Abstract

Ovarian cancer (OC) is the most lethal gynecological malignancy and is responsible for most gynecological cancer deaths. Apart from conventional surgery, chemotherapy, and radiotherapy, chimeric antigen receptor-modified T (CAR-T) cells as a representative of adoptive cellular immunotherapy have received considerable attention in the research field of cancer treatment. CARs combine antigen specificity and T-cell-activating properties in a single fusion molecule. Several preclinical experiments and clinical trials have confirmed that adoptive cell immunotherapy using typical CAR-engineered T cells for OC is a promising treatment approach with striking clinical efficacy; moreover, the emerging CAR-Ts targeting various antigens also exert great potential. However, such therapies have side effects and toxicities, such as cytokine-associated and "on-target, off-tumor" toxicities. In this review, we systematically detail and highlight the present knowledge of CAR-Ts including the constructions, vectors, clinical applications, development challenges, and solutions of CAR-T-cell therapy for OC. We hope to provide new insight into OC treatment for the future.

Keywords: T lymphocyte; chimeric antigen receptor; immunotherapy; ovarian neoplasms; toxicity.

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Conflict of interest statement

CONFLICTS OF INTEREST No potential conflicts of interest relevant to this article is reported.

Figures

Figure 1
Figure 1. Evolution of CARs
CAR 1° represents the first-generation CARs; an scFv links the CD3ζ or FcεRIγ in the transmembrane region. CAR 2° represents the second-generation CARs; costimulatory molecules such as CD28 are engineered to the signal-transduction region. CAR 3° represents the third-generation CARs; they contain two costimulatory domains. CAR 4° (also called TRUCK) represents the fourth-generation CARs; they are additionally modified using a constitutive or inducible expression cassette for a transgenic protein (e.g., a cytokine), which is released by the CAR-T-cell to modulate T-cell response.
Figure 2
Figure 2. Schematic of MUC16 structure
The full-length MUC16 contains a large cleaved and released domain named CA125 consisting of multiple repeat sequences, followed by a conserved cytoplasmic domain MUC16ecto including a nonrepeating ectodomain, a transmembrane domain, and a cytoplasmic tail.
See this image and copyright information in PMC

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