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.
- 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.
- 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. N. Engl J Med. 2021 Nov 18;385(21):1929-1940.
- Escobar G, Barbarossa L, Barbiera G, Norelli M, Genua M, Ranghetti A, Plati T, Camisa B, Brombin C, Cittaro D, Annoni A, Bondanza A, Ostuni R, Gentner B$, Naldini L$. Interferon gene therapy reprograms the leukemia microenvironment inducing protective immunity to multiple tumor antigens.Nat Commun. 2018 Jul 24;9(1):2896.
- Brown BD*, Gentner B*, Cantore A, Colleoni S, Amendola M, Zingale A, Baccarini A, Lazzari G, Galli C, Naldini L. Endogenous microRNA can be broadly exploited to regulate transgene expression according to tissue, lineage and differentiation state. Nat Biotechnol. 2007 Dec;25(12):1457-67.
Pr Bernhard Gentner is the the most recent PI to join the Department of oncology UNIL CHUV as group leader within the Hi-TIDe.
His lab pages are currently under construction and we hope to provide you with a full insight into the research his group will be conducting very shortly.
In the meanwhile, you can already consult his full publications listing and his affiliations. Two open lab positions currently exist and you can read about those via the links under the "People" section. Should you need any further information, feel free to get in touch with Pr Gentner via the contact details on this page.
The Gentner Lab is currently recruiting Post-docs, PhD candidates and Research assistants.
Please consult our open positions on the Lausane University Hospital website, links below:
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