Anti‐tumor efficacy of human anti‐c‐met CAR‐T cells against papillary renal cell carcinoma in an orthotopic model

Mori, Jun‐ich; Adachi, Keishi; Sakoda, Yukimi; Sasaki, Takahiro; Goto, Shunsuke; Matsumoto, Hiroaki; Nagashima, Yoji; Matsuyama, Hideyasu; Tamada, Koji

doi:10.1111/cas.14835

Cited by 26 publications

(22 citation statements)

References 63 publications

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“…Jun-Ich Mori Et al. ( 25 ) also combined c-Met-CAR-T cells with axitinib, which once again demonstrated that molecular targeted drugs can synergically enhance the antitumor efficacy of CAR-T cells. Preclinical trials using CAR-T cells in combination with chemotherapy and radiation for PCa have shown significant mutually reinforcing effects ( 28 , 30 ).…”

Section: Discussionmentioning

confidence: 96%

“…Furthermore, Jun-Ich Mori et al. ( 25 ) constructed c-Met-targeted CAR-T cells and validated the antitumor efficacy of c-Met-CAR-T cells in situ mouse models derived from clinical renal papillary cell carcinoma tissues. The c-Met-CAR-T cells have been demonstrated to infiltrate tumor tissues and inhibit tumor growth.…”

Section: Car-t Cells For Urologic Neoplasmsmentioning

confidence: 99%

“…Jun-Ich Mori et al. ( 25 ) also evaluated the anti-RCC efficacy of c-MET-CAR-T cells in combination with axitinib, and found that axitinib synergically enhanced the anti-tumor efficacy of CAR-T cells. It suggests that CAR-T cells combined with targeted drugs may also be a way to treat solid tumors in the future.…”

Section: Car-t Cells For Urologic Neoplasmsmentioning

confidence: 99%

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CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future

et al. 2022

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In recent years, with the breakthrough of CAR-T cells in the treatment of hematological tumors, they are increasingly being used to treat solid tumors, including urologic neoplasms. There are many relatively specific targets for urologic neoplasms, especially prostate cancer. Besides, urologic neoplasms tend to progress more slowly than tumors in other organs of the body, providing ample time for CAR-T cell application. Therefore, CAR-T cells technology has inherent advantages in urologic neoplasms. CAR-T cells in the treatment of urologic neoplasms have been extensively studied and preliminary achievements have been made. However, no breakthrough has been made due to the problems of targeting extra-tumor cytotoxicity and poor anti-tumor activity. we systematacially summarized the research actuality of CAR-T cells in urologic neoplasms, discussed the potential value and difficulties of the research. The application of CAR-T cells in the treatment of urologic neoplasms requires improvement of function through screening for better targets, modification of CAR structures, or in combination with other antitumor approaches.

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Section: Discussionmentioning

confidence: 96%

Section: Car-t Cells For Urologic Neoplasmsmentioning

confidence: 99%

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CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future

et al. 2022

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“…In a human c-Met–expressing mesothelioma xenograft in NOD SCID immunodeficient mice, c-Met CAR-T cells produced tumor regression 88 . c-Met CAR-T cells have also demonstrated antitumor activity in NSCLC, renal cell, and gastric epithelial cancer models 89–91 . In a phase 0 study (NCT01837602) in 6 patients with metastatic breast cancer, intratumoral injection of mRNA-transfected c-Met CAR-T cells was tolerated and evoked an inflammatory response within tumors 92 .…”

Section: Targeting the Hgf/c-met Pathwaymentioning

confidence: 99%

c-Met Signaling as a Therapeutic Target in Head and Neck Cancer

Centuori

Bauman

2022

Cancer J

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Despite a dearth of activating driver mutations in head and neck squamous cell carcinoma (HNSCC), aberrant activation of the oncogenes, epidermal growth factor receptor (EGFR), and c-Met is near-universal in human papillomavirus (HPV)–negative disease. Although EGFR activation drove the successful development of the anti-EGFR monoclonal antibody cetuximab in HNSCC, no c-Met–targeting therapy has gained regulatory approval. Inhibition of the c-Met pathway may subvert oncogenesis within the tumor-intrinsic compartment, blocking tumoral proliferation, invasion, migration, and metastasis, or the tumor-extrinsic compartment, modulating the immunosuppressive tumor microenvironment. This review discusses the rationale and current drug development strategies for targeting c-Met or its exclusive ligand hepatocyte growth factor (HGF) in HNSCC.

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“…Akihiro Ishikawa and Masazumi Waseda contributed equally to this work. Podoplanin (PDPN) is a mucin-type transmembrane protein with a glycosylated extracellular domain that is overexpressed in various cancers, such as brain, oral, and lung cancers (Breiteneder-Geleff et al, 1997;Chu et al, 2005;Kahn et al, 2002;Kato et al, 2003Kato et al, , 2004Mishima et al, 2006;Schacht et al, 2005), and is considered a promising therapeutic target for cancer treatment (Kreppel et al, 2010;Mori et al, 2021;Waseda & Kaneko, 2020). To target PDPN, we previously focused on the rat anti-human PDPN antibody (NZ-1), which recognizes PDPN specifically (Kato et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Improved anti‐solid tumor response by humanized anti‐podoplanin chimeric antigen receptor transduced human cytotoxic T cells in an animal model

et al. 2022

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Recently, research has been conducted with chimeric antigen receptor (CAR)‐T cells to improve efficacy against solid tumors. Humanized CAR improved the long‐term survival of CAR‐T cells in patients' peripheral blood, resulting in increased therapeutic efficacy. Therefore, the humanization of the CAR‐gene sequence is considered an effective method. Podoplanin (PDPN) is a glycosylated transmembrane protein that is highly expressed in solid tumors and is associated with poor prognosis in patients with cancer. Therefore, PDPN is considered a biomarker and good target for cancer treatment with CAR‐T cells. Previously, an anti‐PDPN CAR was generated from a conventional nonhumanized antibody—NZ‐1, the only anti‐PDPN antibody for which a CAR was produced. In this study, we investigated other anti‐PDPN CARs from the antibody NZ‐27, or humanized NZ‐1, to enhance the therapeutic potential of CAR‐T cells. The CAR signal intensity was enhanced by the efficient expression of CAR proteins on the T‐cell surface of NZ‐27 CAR‐T cells, which show tumor‐specific cytotoxicity, proinflammatory cytokine production, and anti‐tumor activity against PDPN‐expressing tumor xenografts in mice that were significantly better than those in nonhumanized NZ‐1 CAR‐T cells.

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Anti‐tumor efficacy of human anti‐c‐met CAR‐T cells against papillary renal cell carcinoma in an orthotopic model

Cited by 26 publications

References 63 publications

CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future

CAR-T Cells in the Treatment of Urologic Neoplasms: Present and Future

c-Met Signaling as a Therapeutic Target in Head and Neck Cancer

Improved anti‐solid tumor response by humanized anti‐podoplanin chimeric antigen receptor transduced human cytotoxic T cells in an animal model

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