Prostate cancer is a significant public health problem, and the most commonly diagnosed cancer in the USA. The long natural history of prostate cancer, the presence of a serum biomarker that can be used to detect very early recurrences, and the previous identification of multiple potential tissue-specific target antigens are all features that make this disease suitable for the development of anti-tumor vaccines. To date, many anti-tumor vaccines have entered clinical testing for patients with prostate cancer, and some have demonstrated clinical benefit. DNA vaccines represent one vaccine approach that has been evaluated in multiple preclinical models and clinical trials. The safety, specificity for the target antigen, ease of manufacturing and ease of incorporating other immune-modulating approaches make DNA vaccines particularly relevant for future development. This article focuses on DNA vaccines specifically in the context of prostate cancer treatment, focusing on antigens targeted in preclinical models, recent clinical trials and efforts to improve the potency of these vaccines.
"The success achieved in these studies resulted in exploration of application of DNA vaccine in PCa patients. To our knowledge, no naked DNA vaccine has been used in a randomised clinical trial to date . However, DNA vaccines have been used in phase I/II clinical trials including patients with PCa (Table 1). "
[Show abstract][Hide abstract] ABSTRACT: Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa.
"Immunotherapy has been utilized in oncology over many decades, but only relatively recently has an autologous cellular immunotherapy agent (sipuleucel-T) been approved for clinical use in prostate cancer . Though many attempts at utilizing immunotherapy in PC have focused on PSA [82, 83], as discussed, PSMA is an attractive target based on its restricted sites of expression. Multiple vaccine approaches have been utilized in preclinical models and have moved to early-stage clinical trials [83–88]. "
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer (PC) is the most common noncutaneous malignancy affecting men in the US, leading to significant morbidity and mortality. While significant therapeutic advances have been made, available systemic therapeutic options are lacking. Prostate-specific membrane antigen (PSMA) is a highly-restricted prostate cell-surface antigen that may be targeted. While initial anti-PSMA monoclonal antibodies were suboptimal, the development of monoclonal antibodies such as J591 which are highly specific for the external domain of PSMA has allowed targeting of viable, intact prostate cancer cells. Radiolabeled J591 has demonstrated accurate and selective tumor targeting, safety, and efficacy. Ongoing studies using anti-PSMA radioimmunotherapy with (177)Lu-J591 seek to improve the therapeutic profile, select optimal candidates with biomarkers, combine with chemotherapy, and prevent or delay the onset of metastatic disease for men with biochemical relapse. Anti-PSMA monoclonal antibody-drug conjugates have also been developed with completed and ongoing early-phase clinical trials. As PSMA is a selective antigen that is highly overexpressed in prostate cancer, anti-PSMA-based immunotherapy has also been studied and utilized in clinical trials.
Advances in Urology 01/2012; 2012(5):973820. DOI:10.1155/2012/973820
[Show abstract][Hide abstract] ABSTRACT: Considerable progress has been made in prostate cancer immunotherapy over the last year, and two agents have completed phase III testing. This review will discuss the most promising immune-directed strategies in development for prostate cancer, outlining interventions that mitigate tumor-induced tolerance and highlighting several combination immunotherapy approaches.
A pivotal phase III study using Sipuleucel-T, an autologous prostatic acid phosphatase (PAP)-loaded dendritic cell immunotherapy, in men with metastatic castration-resistant prostate cancer (CRPC) demonstrated a survival advantage over placebo. By contrast, two phase III studies of GVAX, an allogeneic tumor cell vaccine, in a similar patient population failed to show a survival benefit of GVAX or GVAX/docetaxel over standard docetaxel/prednisone. Other strategies currently in clinical development include the ProstVac poxviral vaccine, a PAP-encoding DNA vaccine, and immune checkpoint inhibitory approaches.
Although Sipuleucel-T may receive FDA approval for patients with metastatic CRPC, challenges remain in identifying immunotherapy strategies that overcome immune tolerance, especially when disease burden is substantial. An emerging paradigm focuses on using immunotherapy together with checkpoint antagonists or in combination with conventional therapies in patients with early-stage disease. Such approaches are likely to yield optimal results, but must carefully be explored in well designed phase II studies before moving forward.
Current opinion in urology 02/2010; 20(3):241-6. DOI:10.1097/MOU.0b013e3283381793 · 2.33 Impact Factor
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