Combinatorial strategies for alleviation of tumor-associated immune suppression and therapeutic vaccination against ovarian cancer.

摘要

The prospects for development of therapeutic cancer vaccines have enjoyed a renaissance in recent years, with further encouragement accruing from the US FDA's approval in 2010 of Provenge~R (Dendreon Corporation, Seattle, WA, USA), an autologous dendritic cell (DC) vaccine for prostate cancer. Provenge was the first active cellular therapy to reach the market, breaking through what was widely perceived to be a glass ceiling for cellular therapeutics and cancer vaccines. This renewed optimism has also been fuelled by advances in our knowledge of the mechanisms of immune regulation in the tumor microenvironment. This is particularly true for ovarian cancer, which represents a paradigm for self-defense against immunological attack. Although ovarian cancer recruits multiple mechanisms of immune suppression, thus presenting a formidable barrier to effective tumor vaccination, an understanding of these mechanisms may yield opportunities for adjuvant treatments that counterbalance immune suppression and promote vaccine-induced antitumor immunity.