Cancer vaccines at an inflexion point: what next?

With the approval of the first therapeutic cancer vaccines for veterinarian and human use, the field reached a significant milestone after a considerable interval of tumultuous research and development marked by numerous ups and downs. As the mechanism of action and clinical benefit afforded by this class of agents are starkly different from that of conventional or small targeted therapies for cancer, there are still numerous hurdles that need to be overcome to fully unleash their potential. These challenges and efforts are illustrated in a book just published on this subject, a non-exhaustive yet representative synopsis of the latest advances in cancer vaccine technologies in various stages of development. Major lessons resulting from clinical testing of cancer vaccines and other immune interventions, are being integrated in novel, cutting edge platform technologies that blur the distinction between passive and active immunotherapies as well as carry the promise of fundamentally changing and improving the management of patients with cancer

Programmed cell death-1 (PD-1) at the heart of heterologous prime-boost vaccines and regulation of CD8⁺T cell immunity

Abstract Developing new vaccination strategies and optimizing current vaccines through heterologous prime-boost carries the promise of integrating the benefits of different yet synergistic vectors. It has been widely thought that the increased immunity afforded by heterologous prime-boost vaccination is mainly due to the minimization of immune responses to the carrier vectors, which allows a progressive build up of immunity against defined epitopes and the subsequent induction of broader immune responses against pathogens. Focusing on CD8+ T cells, we put forward a different yet complementary hypothesis based primarily on the systematic analysis of DNA vaccines as priming agents. This hypothesis relies on the finding that during the initiation of immune response, acquisition of co-inhibitory receptors such as programmed cell death-1 (PD-1) is determined by the pattern of antigen exposure in conjunction with Toll-like receptor (TLR)-dependent stimulation, critically affecting the magnitude and profile of secondary immunity. This hypothesis, based upon the acquisition and co-regulation of pivotal inhibitory receptors by CD8+ T cells, offers a rationale for gene-based immunization as an effective priming strategy and, in addition, outlines a new dimension to immune homeostasis during immune reaction to pathogens. Finally, this model implies that new and optimized immunization approaches for cancer and certain viral infections must induce highly efficacious T cells, refractory to a broad range of immune-inhibiting mechanisms, rather than solely or primarily focusing on the generation of large pools of vaccine-specific lymphocytes.</p