IRST Adoptive CAR T Cell Platform

IRST Adoptive CAR T cell platform focuses its research activity on understanding, characterizing, exploiting and modifying the human adaptive immune response to control and fight human neoplasms (mesothelioma, NET, NSCLC, MM, T-ALL). Our projects take advantage of very advanced technologies available at the IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" and revolve around molecular immunology and immunotherapy. We perform screenings for novel specificities in human tumors via BCR repertoire analyses to identify human targeting antibodies from patients and by phage display technology. Antibody sequences are then used to design CAR constructs to genetically engineer human immune cells and modify their tropism towards tumors. While CAR T cells target antigens physiologically or unappropriately residing at the cell surface, TCRs can intercept neoantigens expressed inside cells and presented on MHC / HLA molecules thereby providing novel opportunities for the development of antitumor immunotherapies. Via TCR repertoire analyses coupled to in vitro biological assays we aim to identify TCRs able to recognize with high affinity tumor associated neoantigens. The Adoptive CAR T cell platform can leverage on both in vitro and in vivo preclinical models to test the activity and specificity of most promising CAR and TCR receptors. We use and develop lenti/retroviral based constructs and CRISPR/Cas9 editing approaches to modify also other biological properties of the cells to promote persistence and efficacy further or to couple immunotherapy with radiotherapy (radiocell theranostics). The platform is also involved in the study of the human adaptive immune response to experimental vaccines via serological and TCR repertoire analyses. With the aim of producing allogeneic ATMPs the platform collaborate with an European international consortium which has isolated, produced and characterize iPSCs to implement academic gene therapy based approaches in EU.