Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer.

Sipuleucel-T (Provenge) (Sip-T) is first -in class as a therapeutic autologous vaccine approved for the treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer. This product is the culmination of decades of basic immunological and prostate cancer investigations and 13 y of clinical trial investigations. Sip-T represents a paradigm shift in cancer therapeutics and represents the first approved autologous therapeutic cancer vaccine, which has demonstrated a survival benefit. The potential benefit of this product is the excellent risk to benefit ratio, which will allow for the combination of this approach with other more toxic therapies. The favorable risk to benefit will also afford the opportunity for trials investigating this product earlier in the disease state and in combination with local therapies. The ability to target more localized or lower volume disease will maximize the therapeutic benefit over a longer period of time. The novelty of the platform of this approach could be used to treat any cancer with a tumor-specific cell surface target. The main product of Sip-T is the re-infusion of a patient's antigen presenting cells from leukapheresis after ex-vivo exposure to a chimeric protein of human GM-CSF and PAP. In metastatic CRPC patients three infusions of these activated cells over a month lead to statistically significant 4.1 mo increase in median survival and a 22.5% reduction in risk of death. The main side effect from this re-infusion of activated immune cells is a "flu-like" syndrome that includes chills, fatigue, fevers, back pain, nausea, joints aches and headaches in decreasing order of frequency. Immune monitoring during the clinical trials also demonstrated a specific cellular and antibody immune response, suggesting the proposed mechanism of adoptive immunotherapy to PAP was behind this survival benefit. This product also serves as a proof of principle for targeted immunotherapy for others cancers with defined cell surface markers. In summary, the approval of Sip-T based on a survival benefit and very tolerable safety profile will 1) enhance our ability to care for men with advanced prostate cancer, 2) allow for further investigations of this approach in combination with others therapies with different mechanisms of action and non-overlapping toxicities, and 3) allow further investigations earlier in the course of the disease.