Immunology, Transplantation and Infectious diseases

Experimental hematology

team-item

Group leader

Chiara Bonini

MORE

The main research focus of the lab is the development, preclinical and clinical validation of T-cell based gene therapy approaches to treat cancer. We started the preclinical and clinical use of suicide gene therapy applied to allogeneic stem cell transplantation (allo-HSCT). This approach aims at benefitting from the graftversus-leukemia potential of allogeneic lymphocytes in the context of allo-HSCT, while selectively controlling graft-versus-host disease, their major complication. Pioneered in IRCCS Ospedale San Raffaele in the ‘90s (Bonini et al., Science 1997), optimized and tested in different academic and industry-sponsored clinical trials, the suicide gene therapy approach obtained approval from EMA in 2016, thus representing the first cell based gene therapy product approved for cancer patients in Europe. The many lessons learned with this first project have been more recently exploited in innovative projects designed to redirect T cell specificity against tumor antigens.

Research activity

Recently we developed the TCR gene editing approach (Provasi, Genovese et al., Nat Med 2012; Mastaglio et al., Blood 2017). With this project we completely substitute T cell specificity by editing the genome of T cells with artificial nucleases and viral vectors, thus generating tumor-specific T lymphocytes.

The Immunomonitoring sub-Unit of the lab is dedicated to the identification of immunological correlates with clinical outcome in the context of allo-HSCT, cellular therapy and gene therapy.

Recently, we showed that central memory (TCM) and memory stem T cells (TSCM) are endowed with high expansion and persistence ability, and innovative protocols for their genetic engineering have been developed (reviewed in Gattinoni et al., Nat Med 2017).

The major aim of the lab today, is to actively participate to the exciting transition of cellular therapy from the investigational phase to the phase of real life by developing and validating innovative cellular therapy products.