We are witnessing a new and pivotal inflexion point in the history of immunotherapy for cancer. It is no longer a question of whether immunotherapy could be effective against cancer, but how to optimize and integrate multiple platform technologies so that we can increase both the rate as well as durability of clinical response. The important lessons learned in the past two decades through the modest performance of cancer vaccines along with the striking clinical effectiveness of ACT and immune checkpoint blockade obliges as to rethink the way we position immunotherapy within the therapeutic armamentarium against cancer. Cancer vaccination as a monotherapy has the highest likelihood of success in minimal residual disease, but its development in this setting must be accompanied by appropriate companion methodologies such as monitoring molecular markers of residual disease to render the clinical trials informative and economical. Beyond this stage, vaccination could be useful in niche indications associated with measurable disease that are definable through specific immune gene signatures associated with immune response permissiveness within the tumor tissue. Another promising opportunity for cancer vaccines is, as a component of integrative approaches, used as a complement to repertoire restoration or repertoire enhancement strategies based on adoptive T-cell therapies with TILs or genetically engineered T cells. While there are some interesting preliminary results, more development needs to be done in terms of leveraging the synergy between ACT, vaccines and immune checkpoint blockade. The next frontier is the design and optimization of integrated immunotherapeutic approaches to achieve prolonged clinical responses in solid tumors, where a number of immune-inhibiting mechanisms converge against immune effector cells.
Expert Rev Vaccines. 2013;12(10):1219-1234. © 2013 Expert Reviews Ltd.