Abstract
Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8+ cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4+ T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.
Highlights
Prostate cancer (PCa) represents the most common noncutaneous cancer and the second leading cause of cancer mortality among men in the United States, with an estimated incidence of 240,890 cases and an estimated number of 33,720 deaths in 2011 [1]
cytotoxic T lymphocytes (CTLs) responses when castrated prior to immunization with an prostate-specific antigen (PSA)-expressing vaccinia virus, providing a rationale of combining vaccination strategies with androgen deprivation. This concept is further supported by the mitigation of CD4+ T cell tolerance to a prostate-restricted model antigen by androgen ablation indicating that specific immunotherapy of PCa may be more efficacious when administered after androgen ablation [42]
Additional human leukocyte antigen (HLA)-A2-restricted prostatic acid phosphatase (PAP)-derived peptides were identified by analyzing pre-existing reactive CD8+ T cells in the blood of PCa patients and healthy donors [73]
Summary
Prostate cancer (PCa) represents the most common noncutaneous cancer and the second leading cause of cancer mortality among men in the United States, with an estimated incidence of 240,890 cases and an estimated number of 33,720 deaths in 2011 [1]. Monoclonal antibodies (mAbs) recognize target structures on the tumor cell surface and mediate their antitumor effects by various mechanisms of action [21]. They are able to efficiently activate the complement system leading to the recruitment of immune cells and tumor cell lysis. MAbs mediate antibody-dependent cellular cytotoxicity (ADCC) by stimulating tumor-reactive immune cells They enhance the uptake of coated tumor cells by phagocytes resulting in an activation of tumor-reactive CD8+ CTLs and CD4+ T cells. Much attention has been paid to the identification of TAAs that represent attractive targets for T cell- or antibody-based immunotherapy
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