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prostate cancer immunotherapy

T J Mai, R Ma, Z Li, S C Bi
Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2 binding, and which has a greater affinity. Fusion of specific antigens to extracellular domain of CTLA4 represents a promising approach to increase the immunogenicity of DNA vaccines. In this study, we evaluated this interesting approach for CTLA4 enhancement on prostate stem cell antigen (PSCA)-specific immune responses and its anti-tumor effects in a prostate cancer mouse model...
October 24, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Chad R Ritch, Michael S Cookson
Docetaxel based chemotherapy showed survival benefit and emerged as the mainstay of treatment for castration resistant prostate cancer (CRPC) in 2004. However, therapeutic options have expanded rapidly since 2011. The spectrum of new agents is broad and includes drugs that target the androgen axis (enzalutamide, abiraterone), immunotherapy (sipuleucel-T), bone seeking radionuclides (radium-223), and second line chemotherapy (cabazitaxel). In addition, new agents have been developed to reduce skeletal related events (denosumab)...
October 17, 2016: BMJ: British Medical Journal
Oladapo Yeku, Susan F Slovin
Immunotherapy for castration-resistant prostate cancer has continued to be an area of active research over the last several years. The enthusiasm of this approach has been based on the assumption of better tolerability and that using the body's own immune system may be more effective than either hormonal or chemotherapy. Sipuleucel-T, a dendritic cell-based vaccine, is the only approved agent in this class for the management of castrate-resistant prostate cancer. Although sipuleucel-T increases overall survival without any significant changes in progression-free survival, other forms of immunotherapy such as PSA-TRICOM, ipilimumab, and chimeric antigen receptor T cell therapy are in advanced stages of clinical development...
September 2016: Cancer Journal
Georgios Gakis, Peter C Black, Bernard H Bochner, Stephen A Boorjian, Arnulf Stenzl, George N Thalmann, Wassim Kassouf
CONTEXT: Urothelial carcinoma is considered a pan-urothelial disease. As such, the remnant urothelium in the upper urinary tract and urethra following radical cystectomy (RC) remains at risk for secondary urothelial tumors (SUTs). OBJECTIVE: To describe the incidence, diagnosis, treatment, and outcomes of patients with SUTs after RC. EVIDENCE ACQUISITION: A systematic search was conducted using PubMed database according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2016 reporting on malignant diseases of the urothelium after RC for bladder cancer...
October 6, 2016: European Urology
Xiao X Wei, Stephen Chan, Serena Kwek, Jera Lewis, Vinh Dao, Li Zhang, Matthew R Cooperberg, Charles J Ryan, Amy M Lin, Terence W Friedlander, Brian Rini, Christopher Kane, Jeffry P Simko, Peter R Carroll, Eric J Small, Lawrence Fong
Granulocytic-macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients with localized prostate cancer undergoing radical prostatectomy. Patients received subcutaneous injections of GM-CSF (250 μg/m(2)/day) daily for 2 weeks (cohort 1; n = 6), 3 weeks (cohort 2; n = 6), or 4 weeks (cohort 3; n = 6)...
September 29, 2016: Cancer Immunology Research
J P Liu, H Wang
Prostate cancer, especially castration-resistant prostate cancer (CRPC) with its very poor prognosis, quite difficult treatments and urgent need of new theraputic strategies has become a serious problem of men's health in our country. Recent studies have shown that prostate cancer cells can stimulate the immune response; therefore, immunotherapy has become one of the hot spots in the treatment of CRPC. Cancer vaccines including polypeptide vaccines, nucleic acid vaccines, whole cell vaccines and autologous dendritic cell vaccines have been in stage Ⅱ or Ⅲ clinical trials, and will have good application prospects...
October 1, 2016: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
Andrea K Miyahira, Sameek Roychowdhury, Sangeeta Goswami, Joseph E Ippolito, Saul J Priceman, Colin C Pritchard, Karen S Sfanos, Sumit K Subudhi, Jonathan W Simons, Kenneth J Pienta, Howard R Soule
INTRODUCTION: The 2016 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond Seed and Soil: Understanding and Targeting Metastatic Prostate Cancer," was held from June 23 to June 26, 2016, in Coronado, California. METHODS: For the 4th year in a row, the Prostate Cancer Foundation (PCF) hosted the CHPCA Meeting, a think tank-structured scientific conference, which focuses on a specific topic of critical unmet need on the biology and treatment of advanced prostate cancer...
September 28, 2016: Prostate
Brian T Rekoske, Douglas G McNeel
Prostate cancer is the most commonly diagnosed cancer, and the second leading cause of cancer-related death for men in the United States. Despite the approval of several new agents for advanced disease, each of these has prolonged survival by only a few months. Consequently, new therapies are sorely needed. For other cancer types, immunotherapy has demonstrated dramatic and durable treatment responses, causing many to hope that immunotherapies might provide an ideal treatment approach for patients with advanced prostate cancer...
September 20, 2016: Cancer
Sarah M Bronner, Jason R Zbieg, James J Crawford
INTRODUCTION: The transcription factor RORγ plays a critical role in the expression of pro-inflammatory cytokine interleukin IL-17 and is therefore an attractive target for the treatment of inflammatory diseases. Interest in this molecular target has been heightened by the advancement of orally and topically administered RORγ modulators into clinical trials. AREAS COVERED: The present review seeks to summarize published patent applications from assignee companies that have disclosed Investigational New Drug (IND) filings for small molecule RORγ/RORγt antagonists and inverse agonists...
September 15, 2016: Expert Opinion on Therapeutic Patents
Boyan Fang, Andrew McKeon, Shannon R Hinson, Thomas J Kryzer, Sean J Pittock, Allen J Aksamit, Vanda A Lennon
Importance: A novel astrocytic autoantibody has been identified as a biomarker of a relapsing autoimmune meningoencephalomyelitis that is immunotherapy responsive. Seropositivity distinguishes autoimmune glial fibrillary acidic protein (GFAP) meningoencephalomyelitis from disorders commonly considered in the differential diagnosis. Objective: To describe a novel IgG autoantibody found in serum or cerebrospinal fluid that is specific for a cytosolic intermediate filament protein of astrocytes...
September 12, 2016: JAMA Neurology
Elizabeth Scheid, Pierre Major, Alain Bergeron, Olivera J Finn, Russell D Salter, Robin Eady, Bader Yassine-Diab, David Favre, Yoav Peretz, Claire Landry, Sebastien Hotte, Som D Mukherjee, Gregory A Dekaban, Corby Fink, Paula J Foster, Jeffery Gaudet, Jean Gariepy, Rafick-Pierre Sekaly, Louis Lacombe, Yves Fradet, Ronan Foley
MUC1 is a glycoprotein expressed on the apical surface of ductal epithelial cells. Malignant transformation results in loss of polarization and overexpression of hypoglycosylated MUC1 carrying truncated carbohydrates known as T or Tn tumor antigens. Tumor MUC1 bearing Tn carbohydrates (Tn-MUC1) represent a potential target for immunotherapy. We evaluated the Tn-MUC1 glycopeptide in a human phase I/II clinical trial for safety that followed a preclinical study of different glycosylation forms of MUC1 in rhesus macaques, whose MUC1 is highly homologous to human MUC1...
October 2016: Cancer Immunology Research
Omid Haji-Ghassemi, Michel Gilbert, Jenifer Spence, Melissa J Schur, Matthew J Parker, Meredith L Jenkins, John E Burke, Henk van Faassen, N Martin Young, Stephen V Evans
Aberrant glycosylation and the overexpression of specific carbohydrate epitopes is a hallmark of many cancers, and tumor-associated oligo-saccharides are actively investigated as targets for immunotherapy and diagnostics. Wisteria floribunda agglutinin (WFA) is a legume lectin that recognizes terminal N-acetylgalactosaminides with high affinity. WFA preferentially binds the disaccharide LacdiNAc (β-D-GalNAc-[1→4]-D-GlcNAc), which is associated with tumor malignancy in leukemia, prostate, pancreatic, ovarian, and liver cancers, and has shown promise in cancer glycobiomarker detection...
September 6, 2016: Journal of Biological Chemistry
Michael E Hurwitz, Joseph Sokhn, Daniel P Petrylak
PURPOSE OF REVIEW: Over the last 10 years, harnessing of the immune system to attack tumors has been one of the major breakthroughs in cancer, primarily through the use of immune checkpoint inhibitors (ICIs). This review will summarize current immune treatments in urologic malignancies and ongoing trials with novel combinations and in different disease settings. RECENT FINDINGS: Patients with urologic malignancies such as kidney and bladder cancer have benefited significantly from these advances with the approval of ICIs in both of these diseases...
November 2016: Current Opinion in Urology
Karim Fizazi
The last 2 years (2014 and 2015) have witnessed major advances in the treatment of genitourinary malignancies. Of note and in marked contrast to previous years, all four major cancers (prostate cancer, testicular cancer, kidney cancer, and bladder cancer) have benefited from this progress. In prostate cancer, it was clearly demonstrated that a local treatment should be administered for high-risk localised disease. The standard of care was changed for patients with upfront metastatic disease with combined androgen deprivation therapy plus docetaxel becoming the new standard for fit patients with multiple bony metastases...
October 2016: European Journal of Cancer
Marinos Tsiatas, Giannis Mountzios, Giuseppe Curigliano
The advent of immunotherapy has transformed the treatment paradigm of several solid tumors and is expected to influence the therapeutic algorithm even more in the future following the results of numerous ongoing clinical trials in a wide range of malignancies. Exploiting the anti-cancer effect of the immune system with the use of vaccines, viral vectors, and more lately with immune check-point inhibitors and chimeric antigen receptor modification, has been proven a successful therapeutic strategy in a broad spectrum of tumors...
July 2016: Annals of Translational Medicine
Marinos Tsiatas, Petros Grivas
Immunotherapy has traditionally been a critical component of the cancer treatment armamentarium in genitourinary (GU) cancers. It has an established role in the management of carefully selected patients with metastatic renal cell carcinoma (RCC) [e.g., high dose interleukin-2 (IL-2)] and non-muscle invasive bladder cancer (NMIBC) [e.g., intravesical Bacillus Calmette-Guérin (BCG)]. In 2010, the sipuleucel-T vaccine was approved by the FDA for the management of metastatic castration-resistant prostate cancer (mCRPC), based on a phase III trial showing overall survival (OS) benefit compared to placebo...
July 2016: Annals of Translational Medicine
Shaveta Mehta, Tim Illidge, Ananya Choudhury
PURPOSE OF REVIEW: Radiotherapy has the potential to augment the host's immune response to cancer. Urological malignancies are highly immunogenic and the combination of radiotherapy and immunotherapy shows promise. In this review, we discuss the effects of radiotherapy on the cancer immune system and highlight the rationale for using the combined approach in prostate, urothelial and renal cancers. Current clinical studies are summarized emphasising the synergistic effects of the combination and the possibility of improved clinical outcomes...
November 2016: Current Opinion in Urology
Susan F Slovin
PURPOSE OF REVIEW: The purpose of this review is to identify possible reasons why prostate cancer suboptimally responds to immune therapies. RECENT FINDINGS: Interrogation of the intraprostatic milieu suggests that within the normal prostate, foci of tumor can be surrounded by inflammatory cells that may or may not represent foci of immune sensitivity. Whether or not these cells are specific 'immune responders' depends on a multiplicity of factors within the host and intratumoral/stromal milieu...
November 2016: Current Opinion in Urology
James C Evans, Meenakshi Malhotra, John F Cryan, Caitriona M O'Driscoll
Prostate specific membrane antigen (PSMA) otherwise known as glutamate carboxypeptidase II (GCPII) is a membrane bound protein that is highly expressed in prostate cancer and in the neovasculature of a wide variety of tumours including glioblastomas, breast and bladder cancers. This protein is also involved in a variety of neurological diseases including schizophrenia and ALS. In recent years, there has been a surge in the development of both diagnostics and therapeutics that take advantage of the expression and activity of PSMA/GCPII...
November 2016: British Journal of Pharmacology
Jean Hoffman-Censits, Lindsay Wilde
PURPOSE OF REVIEW: Combination immunotherapy has already shown promise in several tumor types, such as melanoma and nonsmall cell lung cancer, and studies are ongoing to evaluate this approach in other malignancies. Trials such as these will only continue to expand as additional immune therapies are shown to have efficacy as single agents in cancer. The purpose of this review is to outline the current landscape of immunotherapy in genitourinary cancer, and to highlight ongoing and pending combination immunotherapy trials in bladder, kidney, and prostate cancers...
November 2016: Current Opinion in Urology
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