0000000000542632
AUTHOR
Marco Cortese
Additional file 3 of Efficacy of CAR-T immunotherapy in MET overexpressing tumors not eligible for anti-MET targeted therapy
Additional file 3: Supplement Table 1. MET gene amplification in different cell lines and primary cells derived from human tumors of different origin.
Additional file 4 of Efficacy of CAR-T immunotherapy in MET overexpressing tumors not eligible for anti-MET targeted therapy
Additional file 4: Supplementary Figure 1. Design and binding properties of DO24 single chain antibody fragments. Supplementary Figure 2. Analysis by flow cytometry of cell surface MET expression. Supplementary Figure 3. Quantitative flow cytometer analysis of surface MET levels in A549 wild type, genetically modified, and not transformed human cells. Supplementary Figure 4. Analysis by flow cytometry of cell surface MET expression in carcinoma cells featuring MET overexpression due to high MET gene copy number. Supplementary Figure 5. Analysis of perforin and granzyme B concentrations in the culture supernatants of T cells co-cultured with target cells expressing different surface MET leve…
Efficacy of CAR-T immunotherapy in MET overexpressing tumors not eligible for anti-MET targeted therapy
Abstract Background Aberrant activation of the MET receptor in cancer is sustained by genetic alterations or, more frequently, by transcriptional upregulations. A fraction of MET-amplified or mutated tumors are sensible to MET targeting agents, but their responsiveness is typically short-lasting, as secondary resistance eventually occurs. Since in the absence of genetic alterations MET is usually not a tumor driver, MET overexpressing tumors are not/poorly responsive to MET targeted therapies. Consequently, the vast majority of tumors exhibiting MET activation still represent an unmet medical need. Methods Here we propose an immunotherapy strategy based on T lymphocytes expressing a Chimeri…
Met inhibition revokes IFNγ-induction of PD-1 ligands in MET-amplified tumours
BACKGROUND: Interferon-induced expression of programmed cell death ligands (PD-L1/PD-L2) may sustain tumour immuneevasion. Patients featuring MET amplification, a genetic lesion driving transformation, may benefit from anti-MET treatment. We explored if MET-targeted therapy interferes with Interferon-gamma modulation of PD-L1/PD-L2 in MET-amplified tumours.METHODS: PD-L1/PD-L2 expression and signalling pathways downstream of MET or Interferon-gamma were analysed in MET-amplified tumour cell lines and in patient-derived tumour organoids, in basal condition, upon Interferon-gamma stimulation, and after anti-MET therapy.RESULTS: PD-L1 and PD-L2 were upregulated in MET-amplified tumour cells up…