The evolving role of immunotherapy in prostate cancer

Abstract

The prognosis for men with metastatic, castration-resistant prostate cancer (CRPC) is limited, and patients have very few treatment options, particularly if the treatment failed with docetaxel (Taxotere). As a result, there is a requirement for novel approaches to therapy. Using immunotherapy to induce immune responses to prostate cancer in preclinical and clinical studies appears to be a valid therapeutic approach. In a pivotal phase III trial, treatment with sipuleucel-T, an autologous cellular vaccine consisting of activated antigen-presenting cells loaded with prostatic acid phosphatase (PAP), gave a median overall survival of 25.8 months compared with 21.7 months for placebo-treated patients, resulting in a 22% relative reduction in the risk of death. Based on these results, sipuleucel-T became the first therapeutic vaccine approved for any type of cancer in the USA. PROSTVAC ® -VF, a poxvirus-based vaccine engineered to present prostate-specific antigen (PSA) and three immune costimulatory molecules, and GVAX, a vaccine consisting of two prostate cancer cell lines (LnCAP and PC3) and genetically modified to secrete granulocyte-macrophage colonystimulating factor (GM-CSF), both showed promising results in phase II studies, although GVAX failed to meet its primary end point of overall survival when compared with docetaxel in a phase III study. T-cell modulation is another potential immunotherapeutic strategy for CRPC. Ipilimumab, an antibody against the cytotoxic T-lymphocyteassociated antigen-4, is being evaluated in phase I/II studies, both alone and in combination with chemotherapy, radiotherapy or GVAX, with activity in prostate cancer. CRPC is one of the few tumour types where immunotherapy is the current standard of care. Further research, however, will be necessary to improve antitumour responses and clinical benefits, including the use of novel combinatorial approaches.

Screening and Characterization of a Novel RNA Aptamer That Specifically Binds to Human Prostatic Acid Phosphatase and Human Prostate Cancer Cells

“…Nevertheless, PAP is an important therapeutic target for PC, as evidenced by the recent success of immunotherapy based on PAP. Provenge, which is based on PAP-charged autologous cells, has been FDAapproved and commercialized (Gerritsen 2012;Kong and Byun, 2013;Sims, 2012). Moreover, a PAP encoded DNA vaccine is currently undergoing clinical trials to prevent and treat PC (Lubaroff, 2012;McNeel et al, 2009) An RNA aptamer is similar to an antibody with a wide range of target recognition sites and a variety of applications.…”

Synthesis and evaluation of naphthalene-based thiosemicarbazone derivatives as new anticancer agents against LNCaP prostate cancer cells

“…The synthesis of thiosemicarbazone derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) was carried out according to the steps depicted in Scheme 1. In the initial step, 4-(naphthalen-1-yl)thiosemicarbazide (A) was synthesized via the reaction of 1-naphtyl isothiocyanate with hydrazine hydrate.…”

“…After it was found that the growth of prostate cancer had been androgensensitive, hormonal therapy was used to treat metastatic disease. At first all patients with prostate cancer responded to hormonal therapy but then the majority gradually developed resistance so it has turned out an obligation to find out new ways for the treatment of prostate cancer [2][3][4][5][6][7][8] . Thiosemicarbazones possess a wide range of pharmacological effects including antineoplastic, antibacterial, antifungal and antiviral activity and they give rise to a great variety of coordination modes depending on their chemical structure.…”

Autophagosome-based strategy to monitor apparent tumor-specific CD8 T cells in patients with prostate cancer

“…40 In the majority of the clinical trials, the focus is on serum PSA responses, humoral responses as well as T cell activation or CD4-responses. 19 , 28 , 29 , 41-44 No autologous tumors were available from the patients from this trial, making it impossible to test whether the CD8 + T cells recognizing antigens in the UbiLT3 DRibble vaccine could also recognize and kill autologous tumor cells. The lack of primary tumor also prevented the search for patient-specific neo-epitopes and CD8 + T cells recognizing such epitopes.…”