This review also discusses the innovative cancer immunotherapies targeting c-MET, including chimeric antigen receptor (CAR) therapies, monoclonal antibodies, and antibody-drug conjugates, while encouraging the development of a comprehensive strategy that simultaneously tackles immune evasion and enhances anti-tumor efficacy further to improve the clinical prognoses for patients with c-MET-positive malignancies. Despite the challenges and variability in efficacy across different cancer subtypes, continued research into the molecular mechanisms and the development of innovative therapeutic strategies will be crucial.

This study provides compelling evidence for the safety and efficacy of CAR-M therapy in treating pancreatic cancer. The results demonstrate that CAR-M-c-MET significantly suppresses pancreatic cancer progression and enhances the effectiveness of cytotoxic chemotherapy. Remarkably, no discernible side effects occur. Further clinical trials are warranted in human pancreatic cancer patients.

We elucidate the therapeutic benefits of CAR T cells in HCC and identify the primary barriers to their broader application. Our analysis aims to provide a comprehensive overview of the current status and future prospects of CAR T-cell immunotherapy for HCC.

PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.

CAR-T cells proliferated specifically under antigenic stimulation, exerting cytotoxic effects on cancer cells and releasing cytokines interleukin 2 (IL-2) and interferon-gamma (IFN-γ), thereby demonstrating the biological functions. Conclusion c-Met may be a promising therapeutic target in COAD; c-Met-targeted CAR-T cells demonstrate inhibitory effects on colorectal cancer cells in vitro.

We found that c-Met is highly expressed in rNPC tissues and confirmed its potential as a CAR-T target for rNPC. Our study provides a new idea for the clinical treatment of rNPC.

Correspondingly, overexpression of c-Met in the embryonic kidney cell line HEK293T led to their enhanced killing by NK1 CAR-T cells. Our studies demonstrate that a minimal amino-terminal polypeptide sequence comprising the kirngle1 domain of HGF is highly relevant to the design of effective CAR-T cell therapies that kill HCC cells expressing high levels of c-Met.

Data evaluating CAR T therapy in patients with solid tumors are limited. This pilot clinical trial demonstrates that intravenous cMET-directed CAR T-cell therapy is safe and feasible in patients with metastatic melanoma and metastatic breast cancer, supporting the continued evaluation of cellular therapy for patients with these malignancies.

This paper firstly discussed the value of c-Met targeted therapy in urologic neoplasms, then summarized the related research progress, and finally explored the potential targets related to the HGF/c-Met signaling pathway. It may provide a new concept for the treatment of middle and late urologic neoplasms.

The regulation of EZH2/SULF1/cMET axis were further validated in patient samples with chondrosarcoma. The results not only established a signal pathway promoting malignancy of chondrosarcoma but also provided a therapeutic potential for further development of effective target therapy to treat chondrosarcoma.

Methods : We developed a HER2-CAR/5D5-T, a T-cell co-expressing a first generation HER2-CAR and a c-MET antibody receptor derived from Onartuzumab (MetMAb; OA-5D5), linked to a 4-1BB co-stimulatory domain...However, the pattern of pro-inflammatory cytokine production (e.g., IL6, TNFα, GMCSF) in conditions with variable densities of target antigen HER2 was moderate, density dependent and distinct from 2 nd generation HER2-CART (Figure 1d-g). Conclusion : Our studies suggest a more favorable functional profile of HER2-CAR/5D5-T and support further testing of strategies to combine c-MET inhibition with CART targeting HER2 or other tumor-associated antigens in sarcoma.

Taken together, we provided useful method to generate c-Met CAR- T cells, which exhibit enhanced cytotoxicity against NSCLC cells in vitro and in vivo. Thus, providing a new therapeutic avenue for treating NSCLC clinically.Highlights (1) c-Met CAR-T capable of stably expressing c-Met CARs were constructed.(2) c-Met CAR-T have strong anti-tumor ability and proliferation ability in vitro.(3) c-Met CAR-T can effectively inhibit the growth of A549 cells subcutaneous xenografts.

Moreover, c-Met-28-137-3ζ CAR-T cells eradicated HCC more effectively in xenograft tumor models compared with the control groups. This study suggests that 3 -generation c-Met CAR-T cells are more effective in inhibiting c-Met-positive HCC cells than 2 -generation c-Met CAR-T cells, thereby providing a promising therapeutic intervention for c-Met-positive HCC.

In an in vivo xenograft assay with NSG bearing MKN-45, a c-Met positive GC cell line, c-Met CAR T cells effectively inhibited the tumor growth of MKN-45. Our results show that the c-Met CAR T cell therapy can be effective on GC.

CAR-Ts target c-Met had no obvious off-target toxicity to normal organs. Thus, the PD1/CD28 CSR could further enhance the anti-tumor ability of c-Met CAR-T, and provides a promising design strategy to improve the efficacy of CAR-T in GC.

P1/2, N=50, Recruiting, Shenzhen BinDeBio Ltd. | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> May 2021

P1, N=77, Terminated, University of Pennsylvania | N=10 --> 77 | Trial completion date: Jul 2020 --> Mar 2020 | Active, not recruiting --> Terminated; Halt in funding