Nouvelles approches vaccinales en cancérologie

Abstract

The concept of cancer vaccine relies on the induction of an adaptive immune response against antigens presented by tumor cells, in order to allow a long-term control of the tumor. First generations of cancer vaccines have been associated with relatively disappointing clinical results. The therapeutic breakthrough provided by the immune checkpoint inhibitors targeting PD-1/PD-L1, and the demonstration of the key role played by mutation-associated neoantigens in anti-tumor T cell response, have led to a renaissance of cancer vaccination. This next generation of cancer vaccines is thus based on the use of mutated neoantigens specific to each tumor (personalized approach). Preclinical results have shown that these neoantigens are able to induce potent antitumor immune responses, explained by the absence of thymic selection against the reactive T cells. Several clinical trials are ongoing, with promising preliminary results. Nevertheless, the demonstration of an anti-tumor effect remains to be done in the clinic. The optimization of neoantigen selection process is still a major challenge. Finally, cancer vaccines may either reinforce the activity of anti-PD-1/PD-L1, by increasing the number of effector T cells in the tumor, or induce an adaptive T cell response in non-T cell infiltrated "cold tumors". Vaccination may also have a strong interest in an adjuvant setting to allow a long-term control of the residual disease.

Keywords: Adjuvant; Checkpoints; Neoantigens; Néoantigènes; Vaccin; Vaccine.