
Immunotherapeutic strategies for solid tumours: discovery and validation of novel targets for CAR and TCR adoptive cell transfer

In the past decade, immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, significantly improving outcomes for many patients. However, despite their remarkable efficacy, a substantial proportion of patients do not respond to ICIs or become resistant. One major limitation is the insufficient presence of tumour-specific effector T cells within the tumour microenvironment, leading to a weak endogenous antitumour response.
Advancement in T cell engineering techniques has led to the development of immunotherapy based on adoptive cell transfer (ACT), which consists in the infusion of tumour-reactive T cells. Several ACT approaches, including T-cell based therapies genetically modified to express chimeric antigen receptor (CAR) and T cell receptor (TCR), have emerged, offering new therapeutic options for the treatment of haematological and solid cancers.
In this talk, I will present 1) a platform for discovering novel tumour targets for CAR- or TCR-based therapies; 2) preclinical validation of two CARs targeting osteosarcoma; 3) preclinical evaluation of a therapeutic TCR transiently expressed in T cells by mRNA electroporation and targeting a public neoantigen; 4) along with strategies to enhance safety and efficacy.