Next-generation cancer vaccine approaches: integrating lessons learned from current successes with promising biotechnologic advances

DT Le, EM Jaffee - Journal of the National Comprehensive Cancer …, 2013 - jnccn.org
Journal of the National Comprehensive Cancer Network, 2013jnccn.org
With the recent approval of sipuleucel-T for metastatic castration-resistant prostate cancer
and ipilimumab for metastatic melanoma, there is increasing excitement in the field of cancer
immunotherapy. A large number of clinical trials are currently testing various vaccine vectors
in a diverse array of cancer types. Which of these strategies will ultimately prove successful
has yet to be determined. However, a better understanding of the complex interplay of tumor-
specific T cells and the challenges faced at the tumor microenvironment, advances in …
With the recent approval of sipuleucel-T for metastatic castration-resistant prostate cancer and ipilimumab for metastatic melanoma, there is increasing excitement in the field of cancer immunotherapy. A large number of clinical trials are currently testing various vaccine vectors in a diverse array of cancer types. Which of these strategies will ultimately prove successful has yet to be determined. However, a better understanding of the complex interplay of tumor-specific T cells and the challenges faced at the tumor microenvironment, advances in biotechnology, and lessons learned from prior successes and failures will likely lead to approvals of other therapeutic cancer vaccines.
With the approvals of sipuleucel-T and ipilimumab, immunotherapy has become a treatment option for more oncology patients. Sipuleucel-T is an autologous cellular product immunotherapy used to prime tumor antigen-specific T cells, and ipilimumab targets cytotoxic T-lymphocyte antigen 4 (CTLA-4) on activated T cells to block negative signals to the T cell. 1-7 Future successes are predicted as a result of blocking a second T-cell inhibitory signaling pathway, programmed death-1 (PD-1) and its ligand PD-L1. 8-10 Furthermore, vaccination with patient-specific hybridoma-derived idiotype vaccine may prolong disease-free survival in patients with follicular lymphoma after chemotherapy-induced remission, 11 and a survival benefit was seen for patients with advanced melanoma treated with gp100 peptide vaccine plus high-dose interleukin 2 (IL-2) over those treated with IL-2 alone. 12 Importantly, the success of sipuleucel-T for prostate cancer and the predicted success of agents that block the PD-1/PD-L1 pathway for non-small cell lung cancer (NSCLC) challenges for the first time the dogma that immunotherapy will only be successful against immunogenic cancers like malignant melanoma. In addition, immune checkpoint inhibitors have received increasing attention because of their ability to produce actual tumor regressions, challenging the long-held belief that immunotherapy will only work well in patients with minimal residual disease. 5, 6, 8, 10 Acceptance of therapeutic vaccines, however, continues to be hampered by questionable proof of activity as single agents. Schlom 13 recently provided an excellent summary of current vaccine platforms, targets, trial design, combinatorial strategies, biomarkers, and future approaches. This article expands on the discussion of recent immunotherapy successes and highlights new advances that will undoubtedly lead to future clinical successes.
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