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https://www.readbyqxmd.com/read/27893426/sublethal-exposure-to-alpha-radiation-223ra-dichloride-enhances-various-carcinomas-sensitivity-to-lysis-by-antigen-specific-cytotoxic-t-lymphocytes-through-calreticulin-mediated-immunogenic-modulation
#1
Anthony S Malamas, Sofia R Gameiro, Karin M Knudson, James W Hodge
Radium-223 dichloride (Xofigo®; 223Ra) is an alpha-emitting radiopharmaceutical FDA-approved for the treatment of bone metastases in patients with advanced castration-resistant prostate cancer. It is also being examined clinically in patients with breast and lung carcinoma and patients with multiple myeloma. As with other forms of radiation, the aim of 223Ra is to reduce tumor burden by directly killing tumor cells. External beam (photon) and proton radiation have been shown to augment tumor sensitivity to antigen-specific CD8+ cytotoxic T lymphocytes (CTLs)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879971/tcr-diversity-a-universal-cancer-immunotherapy-biomarker
#2
EDITORIAL
Douglas G McNeel
Sipuleucel-T was approved as a treatment for men with advanced metastatic, castration-resistant prostate cancer on the basis of improved survival in randomized clinical trials. A major challenge for this therapy, as well as other newer cancer immunotherapy agents, has been to identify markers that can identify patients who benefit from these therapies. In a recent manuscript by Sheikh and colleagues, the investigators evaluated changes in T cell clonality in the peripheral blood and tumors of patients treated with sipuleucel-T using next generation sequencing of T cell receptor Vß CDR3 sequences...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27843208/immunotherapy-in-metastatic-prostate-cancer
#3
REVIEW
Susan F Slovin
INTRODUCTION: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. METHODS: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. RESULTS: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/27836866/sequencing-of-sipuleucel-t-and-androgen-deprivation-therapy-in-men-with-hormone-sensitive-biochemically-recurrent-prostate-cancer-a-phase-ii-randomized-trial
#4
Emmanuel S Antonarakis, Adam S Kibel, Evan Y Yu, Lawrence I Karsh, Aymen Elfiky, Neal D Shore, Nicholas J Vogelzang, John M Corman, Frederick E Millard, Johnathan C Maher, Nancy Chang, Todd DeVries, Nadeem A Sheikh, Charles G Drake
BACKGROUND: STAND, a randomized, phase II, open-label trial (NCT01431391) assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically-recurrent prostate cancer (BRPC) patients at high risk for metastasis. METHODS: Men with BRPC following prostatectomy and/or radiotherapy, a prostate-specific antigen (PSA) doubling time (PSADT)less than or equal to 12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms...
November 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27825118/amplification-of-muc1-in-prostate-cancer-metastasis-and-crpc-development
#5
Nicholas Wong, Pierre Major, Anil Kapoor, Fengxiang Wei, Judy Yan, Tariq Aziz, Mingxing Zheng, Dulitha Jayasekera, Jean-Claude Cutz, Mathilda Jing Chow, Damu Tang
Evidence supports the upregulation of MUC1 in prostate cancer (PC). However, this has not been thoroughly investigated. We report here an association of MUC1 upregulation with PC metastasis and the development of castration resistant PC (CRPC). MUC1 expression was specifically increased in DU145 cell-derived PC stem-like cells (PCSLCs) in comparison to their non-PCSLCs counterparts. While immunohistochemistry staining of 34 primary PCs revealed variability in MUC1 expression, Nanostring technology demonstrated elevated MUC1 mRNA levels in 4 of 7 PCs compared to their normal matched tissues...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27802360/prostate-cancer-developing-novel-approaches-to-castration-sensitive-disease
#6
REVIEW
Edoardo Francini, Mary-Ellen Taplin
Although androgen-deprivation therapy (ADT) remains the mainstay of castration-sensitive prostate cancer (CSPC) therapy, the disease's heterogeneity and the limited duration of the response have chaperoned the introduction of chemotherapy and the investigation of novel hormonal targeted agents in this setting. Combinations of ADT plus chemotherapy or novel hormonal therapies are being tested at various stages of CSPC with promising results. Furthermore, immunotherapy and experimental drugs are also being actively investigated in this setting...
November 1, 2016: Cancer
https://www.readbyqxmd.com/read/27796762/new-biomarkers-for-selecting-the-best-therapy-regimens-in-metastatic-castration-resistant-prostate-cancer
#7
Isabel Heidegger, Axel Heidenreich, David Pfister
Prostate cancer is the most common cancer in men. In recent years, several new targeted therapeutic agents for the treatment of metastatic castration resistant prostate cancer (mCRPC) have been developed. These include androgen receptor targeting agents, new taxanes, radium-223, and immunotherapies. In this short review, we provide a summary of clinical and preclinical biomarkers for each of these new treatment strategies, also including new markers currently presented in conference papers only. Moreover, we address the role of these biomarkers in clinical routine with the aim to select best-personalized treatment strategies for patients...
October 27, 2016: Targeted Oncology
https://www.readbyqxmd.com/read/27783810/construction-of-a-fusion-plasmid-containing-the-psca-gene-and-cytotoxic-t-lymphocyte-associated-antigen-4-ctla-4-and-its-anti-tumor-effect-in-an-animal-model-of-prostate-cancer
#8
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
https://www.readbyqxmd.com/read/27754846/advances-in-the-management-of-castration-resistant-prostate-cancer
#9
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
https://www.readbyqxmd.com/read/27749327/immune-therapy-for-prostate-cancer
#10
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
https://www.readbyqxmd.com/read/27720534/systematic-review-on-the-fate-of-the-remnant-urothelium-after-radical-cystectomy
#11
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
https://www.readbyqxmd.com/read/27688020/systemic-gm-csf-recruits-effector-t-cells-into-the-tumor-microenvironment-in-localized-prostate-cancer
#12
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)...
November 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27686644/-new-progress-of-castration-resistant-prostate-cancer-immunotherapy
#13
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]
https://www.readbyqxmd.com/read/27679977/beyond-seed-and-soil-understanding-and-targeting-metastatic-prostate-cancer-report-from-the-2016-coffey-holden-prostate-cancer-academy-meeting
#14
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
https://www.readbyqxmd.com/read/27649312/immunotherapy-for-prostate-cancer-false-promises-or-true-hope
#15
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...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27629281/ror%C3%AE-antagonists-and-inverse-agonists-a-patent-review
#16
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
https://www.readbyqxmd.com/read/27618707/autoimmune-glial-fibrillary-acidic-protein-astrocytopathy-a-novel-meningoencephalomyelitis
#17
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
https://www.readbyqxmd.com/read/27604597/tn-muc1-dc-vaccination-of-rhesus-macaques-and-a-phase-i-ii-trial-in-patients-with-nonmetastatic-castrate-resistant-prostate-cancer
#18
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
https://www.readbyqxmd.com/read/27601469/molecular-basis-for-recognition-of-the-cancer-glycobiomarker-lacdinac-galnac-%C3%AE-1%C3%A2-4-glcnac-by-wisteria-floribunda-agglutinin
#19
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 oligosaccharides 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...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27584025/cancer-immunotherapy-new-applications-in-urologic-oncology
#20
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
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