Filippo Birocchi
A5063067098- CAR-T cell therapy research
- Pancreatic and Hepatic Oncology Research
- Virus-based gene therapy research
- Heat shock proteins research
- T-cell and B-cell Immunology
- Autophagy in Disease and Therapy
- Immune Cell Function and Interaction
- Immune cells in cancer
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Single-cell and spatial transcriptomics
- Eosinophilic Esophagitis
- Multiple Myeloma Research and Treatments
- Neuroblastoma Research and Treatments
- Esophageal and GI Pathology
- Brain Metastases and Treatment
- Cancer Immunotherapy and Biomarkers
- Viral Infectious Diseases and Gene Expression in Insects
- Tryptophan and brain disorders
- Biosimilars and Bioanalytical Methods
- Nanoplatforms for cancer theranostics
- Cell Adhesion Molecules Research
- Cancer Research and Treatments
Massachusetts General Hospital
2023-2024
Harvard University
2023-2024
The San Raffaele Telethon Institute for Gene Therapy
2020-2022
Istituti di Ricovero e Cura a Carattere Scientifico
2022
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2022
Vita-Salute San Raffaele University
2020-2022
Institute for Experimental Endocrinology and Oncology
2018
National Research Council
2018
Istanbul University
2018
University of Genoa
2016
Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target expression, escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated cancer-associated fibroblasts (CAF), which may contribute limited efficacy of mesothelin-directed CAR in early-phase clinical trials. To provide more favorable TME for pancreatic ductal adenocarcinoma (PDAC), we an antimesothelin secreted...
Glioblastoma multiforme (GBM) is the most common and lethal brain tumor characterized by a strongly immunosuppressive microenvironment (TME) that represents barrier also for development of effective immunotherapies. The possibility to revert this hostile TME immunoactivating cytokines hampered severe toxicity associated with their systemic administration. Here, we exploited lentiviral vector–based platform engineer hematopoietic stem cells ex vivo aim releasing, via tumor-infiltrating...
Persisters are a sub-population of tumor cells that survive anti-cancer therapy facilitating recurrence, and have been identified following drug- immune-therapy but generally considered as distinct entities. Drugs immune often kill via apoptosis, therefore, we tested hypothesis both types based on reduced mitochondrial apoptotic sensitivity, which would yield multi-therapy resistance. We observed IPCs acquired sensitivity to multiple drugs radiotherapy. Likewise, DTPs developed radiotherapy,...
Abstract Macrophages in the tumor microenvironment exert potent anti-tumorigenic activity through phagocytosis. Yet therapeutics that enhance macrophage phagocytosis have not improved outcomes clinical trials for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). To systematically identify regulators of phagocytosis, we performed genome-scale CRISPR knockout screens human cells co-cultured monocyte-derived macrophages. Surprisingly, found whereas classic “don’t eat...
The receptor tyrosine kinase ERBB2 interacts with HSP90 and is overexpressed in aggressive breast cancers. Therapeutic inhibitors, i.e. Geldanamycin (GA), target to degradation. We have previously shown that responsible for the missorting of recycling degradation compartments. In this study, we used biochemical, immunofluorescence electron microscopy techniques demonstrate SKBR3 human cancer cells, GA strongly induces polyubiquitination internalization full-length p185-ERBB2, promotes its...
Abstract Introduction: Antigen heterogeneity is a challenge for CAR-T cell therapy in solid tumors due to antigen escape when targeting single antigen. In ovarian cancer (OC), mesothelin (meso) and Mucin16 (MUC16) are two of the most overexpressed antigens. Moreover, CA125, which part MUC16, lost some OC patients, but ectodomain remains on surface. Targeting both antigens (Meso MUC16ecto) with tandem-CAR configuration could overcome improve efficacy OC. Material Methods: We designed library...
<p>Supplementary Video S2. Meso^FAP CAR T cells on AsPC1</p>
<p>Supplementary Methods</p>
<p>Supplementary Figure S8. Target expression and individual analysis of patient-derived organoids (PDO) with matching CAFs.</p>
<p>Supplementary Figure S6. Human CAF-1 cells do not expand in vivo NSG mice the presence or absence of AsPC-1 PDX1294 cells.</p>
<p>Supplementary Figure S5. Intratumoral multiplex RNA-ISH IF imaging and analysis of CAR-TEAM treated mice.</p>
<p>Supplementary Figure S3. ASPC-1 and CAF repeat stimulation initiates a different transcription profile of meso^FAP meso^CD19 CAR T-cells over time.</p>
<p>Supplementary Video S9. UTD T cells on AsPC1 + CAF</p>
<p>Supplementary Video S1. Meso^FAP CAR T cells on AsPC1 + CAF</p>
<div>AbstractPurpose:<p>Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target expression, escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated cancer-associated fibroblasts (CAF), which may contribute limited efficacy of mesothelin-directed CAR in early-phase clinical trials. To provide more favorable TME for pancreatic ductal adenocarcinoma...
<p>Supplementary Figure S1. Characterization of mesoFAP CAR T-cells compared to control T-cells.</p>
<p>Supplementary Figure S6. Human CAF-1 cells do not expand in vivo NSG mice the presence or absence of AsPC-1 PDX1294 cells.</p>
<p>Supplementary Figure S7. Superior anti-tumor effect of meso^FAP compared to the combination meso-CAR and FAP-CAR or meso^CD19.</p>
<p>Supplementary Figure S4. Still frames from live cell microscopy videos demonstrating reduced edge dynamics of meso^FAP CAR T-cells compared to controls and target layer on flow chamber acoustic microscopy.</p>
<p>Supplementary Video S11. UTD T cells on CAF</p>
<p>Supplementary Figure S2. In vitro setup of CARTEAM to CAF:AsPC-1 with different ratios showing superiority mesoFAP compared CARs targeting mesothelin only.</p>
<p>Supplementary Video S12. UTD T cells not on target</p>