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Strategies to neutralize immunosuppressor mechanisms include chemotherapy (cyclophosphamide), the use of antibodies as a means to diminish regulatory T cells (CD25-targeted antibodies), and the use of antibodies against immune-checkpoint molecules such as CTLA-4 and PD1.
This review summarizes the main strategies in cancer immunotherapy and discusses recent advances in the design of synergistic combination strategies [-Omits the task of breaking tolerance to tumor antigens-Produces a high avidity in effector T cells-Lymphodepleting conditioning regimen prior to TIL infusion enhances efficacy-Genetic T cell engineering broadens TIL to malignancies other than melanoma Historically, the primary approach to specifically activate host T cells against tumor antigens has been therapeutic cancer vaccination.
It is now established that various components of the immune system play pivotal roles in protecting humans from cancer.
This could be attributed to their poor pharmacokinetic properties leading to their rapid clearance before being loaded onto DCs.Early on, it was not appreciated that, by creating an environment that disables the immune response, cancer is able to induce tolerance.Therefore, in contrast to conventional prophylactic vaccines for infectious agents, in order to be effective, cancer vaccination must break the tolerance acquired by the tumor cells .In addition to the successful use of preventative vaccines used in the defense against cancer-causing infectious diseases, including hepatitis B virus and human papillomavirus, the knowledge that patients can harbor CD8 and CD4 T cells capable of recognizing tumor expressed antigens hinted at the possibility of developing cancer vaccines .Unfortunately, the general lack of understanding of the mechanisms of immunization, and particularly of the role of dendritic cells (DCs), has led to a series of failures of therapeutic cancer vaccines in initial randomized trials .