Tandem CAR-T cells targeting FOLR1 and MSLN enhance the antitumor effects in ovarian cancer

Liang, Zhen; Dong, Jiao; Yang, Neng; Li, Si-Di; Yang, Zeyu; Huang, Rui; Li, Fengjie; Wang, Wenting; Ren, Jia-Kui; Lei, Jie; Chen, Zhanghua; Wang, Dan; Wang, Yan-Zhou; Liang, Zhiqing

doi:10.7150/ijbs.63181

Cited by 33 publications

(32 citation statements)

References 35 publications

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“…Based on these results, a phase I clinical trial (NCT03585764) is recruiting patients with ovarian or fallopian tube cancers or primary peritoneal cancers. A recent study described a novel tandem CAR encoding an anti-FRα scFv, an anti-mesothelin scFv, and two peptide sequences of IL-12 to improve the efficacy, infiltration, persistence, and proliferation of CAR T cells in ovarian cancer [ 177 ].…”

Section: Targeting the Tumor Microenvironment In Epithelial Ovarian Cancermentioning

confidence: 99%

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Wallace-Povirk

Hou

Nayeen

et al. 2021

Cancers

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New therapies are urgently needed for epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy. To identify new approaches for targeting EOC, metabolic vulnerabilities must be discovered and strategies for the selective delivery of therapeutic agents must be established. Folate receptor (FR) α and the proton-coupled folate transporter (PCFT) are expressed in the majority of EOCs. FRβ is expressed on tumor-associated macrophages, a major infiltrating immune population in EOC. One-carbon (C1) metabolism is partitioned between the cytosol and mitochondria and is important for the synthesis of nucleotides, amino acids, glutathione, and other critical metabolites. Novel inhibitors are being developed with the potential for therapeutic targeting of tumors via FRs and the PCFT, as well as for inhibiting C1 metabolism. In this review, we summarize these exciting new developments in targeted therapies for both tumors and the tumor microenvironment in EOC.

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Section: Targeting the Tumor Microenvironment In Epithelial Ovarian Cancermentioning

confidence: 99%

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Wallace-Povirk

Hou

Nayeen

et al. 2021

Cancers

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“…Tandem CARs have successfully decreased antigen escape mechanisms in both liquid and solid tumors. [63][64][65] Furthermore, tandem CAR technology is one strategy to address antigen heterogeneity within a tumor.…”

Section: Overcoming T Cell-extrinsic Limitationsmentioning

confidence: 99%

Chimeric Antigen Receptor T-Cell Therapy

Brookens

Posey

2023

Cancer J

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Genetically engineered chimeric antigen receptor (CAR) T-cell therapy leverages the ability of the immune system to eliminate tumors and redirects cytotoxic functions toward cells expressing specified tumor-restricted antigens. Although 6 CAR T-cell therapies have received Food and Drug Administration (FDA) approval for the treatment of many hematological malignancies, limitations involving T cell-intrinsic, T cell-extrinsic, and therapeutic factors remain in the treatment of both liquid and solid tumors. Chimeric antigen receptor design, signals from the tumor microenvironment, tumor antigen escape mechanisms, and systemic inflammatory consequences of CAR T-cell infusion all influence the efficacy and feasibility of CAR T-cell therapy in different malignancies. Here, we review the core structure of the CAR, the evolution of different CAR generations, CAR T-cell therapy limitations, and current strategies being investigated to overcome the T cell-intrinsic, T cell-independent, and therapeutic barriers to successful CAR T-cell therapy.

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“…In addition, in OC in vivo or in vitro studies, CAR therapies targeting FRα, HER2, uPAR, 5 T4, ALPPL2, B7H3, PTK7, TAG72, CD47, OR2H1, and CDH6 have been suggested as promising therapeutic approaches [195,213,306,[333][334][335][336][337][338] (Fig. 3).…”

Section: Ovarian Cancer (Oc)mentioning

confidence: 99%

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

Zhang

Cao

et al. 2022

Mol Cancer

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Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

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Tandem CAR-T cells targeting FOLR1 and MSLN enhance the antitumor effects in ovarian cancer

Cited by 33 publications

References 35 publications

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer

Chimeric Antigen Receptor T-Cell Therapy

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

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