0000000001036974
AUTHOR
Silvia Giordano
Additional file 2 of hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
Additional file 2.
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.
Tumorigenic and metastatic activity of human thyroid cancer stem cells
Abstract Thyroid carcinoma is the most common endocrine malignancy and the first cause of death among endocrine cancers. We show that the tumorigenic capacity in thyroid cancer is confined in a small subpopulation of stem-like cells with high aldehyde dehydrogenase (ALDHhigh) activity and unlimited replication potential. ALDHhigh cells can be expanded indefinitely in vitro as tumor spheres, which retain the tumorigenic potential upon delivery in immunocompromised mice. Orthotopic injection of minute numbers of thyroid cancer stem cells recapitulates the behavior of the parental tumor, including the aggressive metastatic features of undifferentiated thyroid carcinomas, which are sustained by…
Additional file 1 of hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
Additional file 1.
By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy
// Annalisa Petrelli 1,* , Rosachiara Carollo 2,* , Marilisa Cargnelutti 1 , Flora Iovino 2 , Maurizio Callari 3 , Daniela Cimino 4 , Matilde Todaro 2 , Laura Rosa Mangiapane 2 , Alessandro Giammona 2 , Adriana Cordova 2 , Filippo Montemurro 1 , Daniela Taverna 4 , Maria Grazia Daidone 3 , Giorgio Stassi 2,* and Silvia Giordano 1,* 1 University of Torino School of Medicine, Candiolo Cancer Institute-FPO, IRCCS, Str. Provinciale, Candiolo, Torino, Italy 2 Department of Surgical and Oncological Sciences, Cellular and Molecular Pathophysiology Laboratory, University of Palermo, Palermo, Italy 3 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 4 Molecular Biotechnology Center (MBC),…
Additional file 3 of hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
Additional file 3.
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…
Erratum: By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy
Basal-like breast cancer is an aggressive tumor subtype with a poor response to conventional therapies. Tumor formation and relapse are sustained by a cell subset of Breast Cancer Stem Cells (BrCSCs). Here we show that miR-100 inhibits maintenance and expansion of BrCSCs in basal-like cancer through Polo-like kinase1 (Plk1) down-regulation. Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal. It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy. The key role played by miR-100 in breast cancer free-survival is confirmed by the analysis of a cohort of patients' tumors, which sho…
hOA-DN30: a highly effective humanized single-arm MET antibody inducing remission of ‘MET-addicted’ cancers
Abstract Background The tyrosine kinase receptor encoded by the MET oncogene is a major player in cancer. When MET is responsible for the onset and progression of the transformed phenotype (MET-addicted cancers), an efficient block of its oncogenic activation results in potent tumor growth inhibition. Methods Here we describe a molecular engineered MET antibody (hOA-DN30) and validate its pharmacological activity in MET-addicted cancer models in vitro and in vivo. Pharmacokinetics and safety profile in non-human primates have also been assessed. Results hOA-DN30 efficiently impaired MET activation and the intracellular signalling cascade by dose and time dependent removal of the receptor fr…