We develop a lentivirus ex-vivo gene transfer strategy into autologous hematopoietic stem/progenitor cells (HSPCs) to target interferon-αexpression to tumor-infiltrating monocytes/macrophages (Tie2 Expressing Monocytes - TEMs). As a result, a recruitment of tumor-specific cytotoxic Tcells is added to the interferon-α effect.
In contrast to antigen-restricted Chimeric Antigen Receptor T cells (CAR-T), Temferon™ generates immune responses to any TEMs positive tumors.
Using a combination of transcriptional and microRNA-mediated control, TEMs become capable to selectively express interferon-αlimited to the tumor micro environment. Based on these mechanisms, TEMs are armed with a specific drug and can systematically break the tumor immune-tolerance reprogramming the micro environment and generate an immune response.
Genenta has been authorized to enter in a Ph I/II clinical trials in early Multiple Myeloma relapsing and newly diagnosed Glioblastoma tumor patients. The demonstration of Temferon™ safety and of the molecular and biological readouts at the base of the predicted clinical efficacy in these two indications should support the potential development of Temferon™ against a broad range of tumors both as first line and as combination therapy.
LUIGI NALDINI is the Director of the San Raffaele Telethon Institute for Gene Therapy and Professor at the San Raffaele University and Milan, Italy. He has pioneered the development and applications of lentiviral vectors for gene therapy and contributed to advance targeted genome editing in cell and gene therapy. He is member of EMBO, past President of ESGCT, and received the Outstanding Achievement Award from ASGCT in 2014 and from ESGCT in 2015, the Beutler Prize from ASH in 2017 and the 2019 Jeantet-Collen Prize for Translational Medicine.