Gentner Lab
Our focus
Our objective is to apply advanced genetic engineering of hematopoietic stem cells in order to develop breakthrough cell therapies against cancer. Our strategies aim to create synergies between engineered haematopoiesis and adoptive T cell therapies. We boast a parallel clinical development that maximises the exchange between laboratory and bedside.
Our projects
- Together with Pr Luigi Naldini in Milan (Italy), we have developed a hematopoietic stem cell (HSC)-based gene therapy to reprogram the tumor microenvironment (TME) by local interferon release from Tie2 expressing monocytes/macrophages. This treatment is currently being tested in a Phase I/IIa dose escalation study in glioblastoma multiforme patients (NCT03866109).
- We are developing novel strategies to target transgene expression to tumor-infiltrating myeloid cells (TIMs), leveraging on curated single cell data and associated clinical outcomes from early clinical trials. HSC will be engineered with transcriptionally-regulated lentiviral vectors or by gene editing.
- We will then exploit this TIM-specific delivery platform to deploy therapeutic payloads within the TME that synergize with adoptive T-cell therapies (T-cell ACT). Discovery of payloads that program synthetic anti-tumor cell network will be accomplished in collaboration with Hi-TIDe’s T cell systems engineering group and Tumor microenvironment & biomarker discovery group.
- We are setting up a modular HSC transplantation platform in patients with advanced solid cancer, which can be combined with T-cell ACT, generating early human data that will further instruct the design of synthetic anti-tumor cell networks.
- We are continuously innovating genetic HSC engineering. In the framework of a European consortium, we are developing purified HSC cultures, ex vivo expansion, gene/base editing and single cell HSC readouts.
- Naldini MM, Casirati G, Barcella M, Rancoita PMV, Cosentino A, Caserta C, Pavesi F, Zonari E, Desantis G, Gilioli D, Carrabba MG, Vago L, Bernardi M, Di Micco R, Di Serio C, Merelli I, Volpin M, Montini E, Ciceri F, Gentner B. Longitudinal single-cell profiling of chemotherapy response in acute myeloid leukemia. Nat Communication. (2023)
- Gentner B, Tucci F, Galimberti S, Fumagalli F, De Pellegrin M, Silvani P, Camesasca C, Pontesilli S, Darin S, Ciotti F, Sarzana M, Consiglieri G, Filisetti C, Forni G, Passerini L, Tomasoni D, Cesana D, Calabria A, Spinozzi G, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Miglietta S, Zonari E, Cheruku PS, Forni C, Facchini M, Corti A, Gabaldo M, Zancan S, Gasperini S, Rovelli A, Boelens JJ, Jones SA, Wynn R, Baldoli C, Montini E, Gregori S, Ciceri F, Valsecchi MG, la Marca G, Parini R, Naldini L, Aiuti A, Bernardo ME. Hematopoietic Stem and Progenitor Cell Gene Therapy for Hurler Syndrome. New. Engl Journal Med. (2021)
- Mucci A, Antonarelli G, Caserta C, Vittoria FM, Desantis G, Pagani R, Greco B, Casucci M, Escobar G, Passerini L, Lachmann N, Sanvito F, Barcella M, Merelli I, Naldini L, Gentner B. Myeloid cell-based delivery of IFN-γ reprograms the leukemia microenvironment and induces anti-tumoral immune responses. EMBO Mol Med. (2021)
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