Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

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.

PSMA targeted docetaxel-loaded superparamagnetic iron oxide nanoparticles for prostate cancer

“…Among all PC cell surface proteins (prostate stem cell antigen, prostein, T cell receptor gamma alternate reading frame protein, six-transmembrane epithelial antigen of the prostate 1, and PSMA), PSMA is a cell-surface protein that is highly overexpressed in almost all prostate cancers and within the tumor neovasculature of other solid tumors [28]. Moreover, FDA-approved anti-PSMA antibody is a prostate-specific imaging agent and a target for the delivery of PC therapeutic agents [29, 30].…”

“…Among many cell-surface protein markers, prostate specific membrane antigen (PSMA) is highly overexpressed in prostate cancers [28], and thus it is considered a valid target for PC [29, 30]. In addition, anti-PSMA antibody or PSMA-specific aptamers A10-3.2 aptamer based targeting and imaging have been tested on patients with PC [29, 31, 32].…”

Screening of Multiple Myeloma by Polyclonal Rabbit Anti-Human Plasmacytoma Cell Immunoglobulin

“…Hundreds of candidate TAAs have been identified in various human cancer types [8], including liver cancer, breast cancer [9], prostate cancer [10], ovarian cancer [11], renal cancer [12], head and neck cancer [13], esophageal cancer [14], lymphoma [15], gastric cancer [16]and leukemia [17].…”

Convergence of Immunotherapy, Radiotherapy and Prostate Cancer: Challenges and Opportunities

“…It has been suggested that the low mutational burden of prostate cancer limits the immunogenicity of the tumor [9]. Prostate cancer does, however have many public tissue-associated antigens, including PSA, PMSA, prostatic alkaline phosphatase (the target of sipuleucel-T) and NY-ESO, and there are a variety of Phase I studies examining the potential to target these antigens to elicit an immune response [10]. It is increasingly recognized that tumors undergo a process of adaptive immunoediting which allows the selection and outgrowth of subclones that can grow in an immunocompetent host [11].…”