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.