0000000001036971
AUTHOR
Lara Fontani
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.
Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody
The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable…
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…