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Immunotherapy prostate

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https://www.readbyqxmd.com/read/29673712/update-on-systemic-prostate-cancer-therapies-management-of-metastatic-castration-resistant-prostate-cancer-in-the-era-of-precision-oncology
#1
REVIEW
Philipp Nuhn, Johann S De Bono, Karim Fizazi, Stephen J Freedland, Maurizio Grilli, Philip W Kantoff, Guru Sonpavde, Cora N Sternberg, Srinivasan Yegnasubramanian, Emmanuel S Antonarakis
CONTEXT: Introduction of novel agents for the management of advanced prostate cancer provides a range of treatment options with notable benefits for men with metastatic castration-resistant prostate cancer (mCRPC). At the same time, understanding of optimal patient selection, effective sequential use, and development of resistance patterns remains incomplete. OBJECTIVE: To review current systemic therapies and recent advances in drug development for mCRPC and strategies to aid in patient selection and optimal sequencing...
April 16, 2018: European Urology
https://www.readbyqxmd.com/read/29665853/microsatellite-instability-in-prostate-cancer-by-pcr-or-next-generation-sequencing
#2
Jennifer A Hempelmann, Christina M Lockwood, Eric Q Konnick, Michael T Schweizer, Emmanuel S Antonarakis, Tamara L Lotan, Bruce Montgomery, Peter S Nelson, Nola Klemfuss, Stephen J Salipante, Colin C Pritchard
BACKGROUND: Microsatellite instability (MSI) is now being used as a sole biomarker to guide immunotherapy treatment for men with advanced prostate cancer. Yet current molecular diagnostic tests for MSI have not been evaluated for use in prostate cancer. METHODS: We evaluated two next-generation sequencing (NGS) MSI-detection methods, MSIplus (18 markers) and MSI by Large Panel NGS (> 60 markers), and compared the performance of each NGS method to the most widely used 5-marker MSI-PCR detection system...
April 17, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29644451/emerging-therapies-in-metastatic-prostate-cancer
#3
REVIEW
Daniel W Sonnenburg, Alicia K Morgans
PURPOSE OF REVIEW: In the last decade, there have been multiple landmark therapeutic advances for the treatment of metastatic prostate cancer, both in the castration-resistant and hormone-sensitive setting. In this review, we highlight recent progress and ongoing trials for metastatic prostate cancer, including advances in chemotherapy, androgen receptor-directed therapy, targeted therapies, and immunotherapy. RECENT FINDINGS: Several landmark studies for men with metastatic hormone-sensitive prostate cancer demonstrated improvement in overall survival with the addition of docetaxel chemotherapy or abiraterone acetate to standard androgen deprivation therapy...
April 11, 2018: Current Oncology Reports
https://www.readbyqxmd.com/read/29621897/current-and-potential-targets-for-drug-design-in-the-androgen-receptor-pathway-for-prostate-cancer
#4
Achuta Kumar Guddati
Modulating the androgen axis by different agents has been one of the most successful therapeutic interventions in the field of prostate cancer therapy. Newer agents such as abiraterone and enzalutamide have been widely adapted and have contributed to an increase in the overall survival of prostate cancer patients. However, most of these patients will develop resistance to these agents and will need chemotherapy. Areas covered: In this review, this author discusses current agents which modulate the androgen axis, the mechanisms of resistance to these agents and investigative agents which are designed to bypass these mechanisms of resistance...
April 6, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29582792/perspectives-on-the-clinical-development-of-immunotherapy-in-prostate-cancer
#5
Lisa M Cordes, James L Gulley, Ravi A Madan
Despite impressive survival benefits with immunotherapy in patients with various solid tumors, the full potential of these agents in prostate cancer has yet to be realized. Sipuleucel-T demonstrated a survival benefit in this population, indicating that prostate cancer is an immunoresponsive disease; however, these results have not been matched by other agents. A large trial with ipilimumab in prostate cancer failed to meet its primary objective, and small trials with PD-1/PD-L1 inhibitors did not yield a significant improvement in overall response...
March 27, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29569115/-systemic-immune-checkpoint-inhibition-a-promising-treatment-for-urological-tumors
#6
REVIEW
F C Roos, C Becker, M B Stope, I Tsaur
Improved understanding of the immunomodulatory interactions between tumor cells and immune cells has led to new and promising systemic therapeutic approaches in the first- and second-line therapy of urological tumors. Particularly in the case of urothelial carcinoma, for the first time in 20 years, checkpoint inhibitors (PD-1 and PDL-1 inhibitors) provide well-tolerated therapy that achieves response rates of >20% that can be sustained over the long term. This review explains the approach of immunotherapy and summarizes the current phase III clinical situation on urothelial carcinoma and renal cell carcinoma...
March 22, 2018: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29554212/combined-immunotherapy-encompassing-intratumoral-poly-iclc-dendritic-cell-vaccination-and-radiotherapy-in-advanced-cancer-patients
#7
M E Rodríguez-Ruiz, J L Perez-Gracia, I Rodríguez, C Alfaro, C Oñate, G Pérez, I Gil-Bazo, A Benito, S Inogés, A López-Diaz de Cerio, M Ponz-Sarvise, L Resano, P Berraondo, B Barbés, S Martin-Algarra, A Gúrpide, M F Sanmamed, C de Andrea, A M Salazar, I Melero
BACKGROUND: Combination immunotherapy has the potential to achieve additive or synergistic effects. Combined local injections of dsRNA analogues (mimicking viral RNA) and repeated vaccinations with tumor-lysate loaded dendritic cells shows efficacy against colon cancer mouse models. In the context of immunotherapy, radiotherapy can exert beneficial abscopal effects. PATIENTS AND METHODS: In this two-cohort pilot phase I study, 15 advanced cancer patients received two 4-week cycles of four intradermal daily doses of monocyte-derived dendritic cells preloaded with autologous tumor lysate and matured for 24h with poly-ICLC (Hiltonol), TNF-α and IFN-α...
March 14, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29553949/recent-advances-in-the-management-of-metastatic-prostate-cancer-optimizing-use-of-existing-therapies-while-searching-for-novel-interventions
#8
Theodore Gourdin
PURPOSE OF REVIEW: Summarizes recent advances in the treatment of metastatic castration-sensitive and castration-resistant prostate cancer. RECENT FINDINGS: New randomized data suggest a survival advantage to early abiraterone in castration-sensitive metastatic prostate cancer. Prospective and retrospective studies are examining sequencing of existing cytotoxic and androgen-receptor-targeted therapies in both castration-sensitive and castration-resistant disease...
May 2018: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29553053/bone-targeted-therapies-to-reduce-skeletal-morbidity-in-prostate-cancer
#9
Tanya B Dorff, Neeraj Agarwal
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA...
March 16, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29548065/immunotherapy-for-prostate-cancer-where-do-we-go-from-here-part-1-prostate-cancer-vaccines
#10
Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/29528821/lynch-syndrome-genomics-update-and-imaging-review
#11
Veronica L Cox, Anas A Saeed Bamashmos, Wai Chin Foo, Shiva Gupta, Sireesha Yedururi, Naveen Garg, Hyunseon Christine Kang
Lynch syndrome is the most common hereditary cancer syndrome, the most common cause of heritable colorectal cancer, and the only known heritable cause of endometrial cancer. Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate. The oncogenic tendency of Lynch syndrome stems from a set of genomic alterations of mismatch repair proteins. Defunct mismatch repair proteins cause unusually high instability of regions of the genome called microsatellites...
March 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
https://www.readbyqxmd.com/read/29523597/cross-talk-between-myeloid-derived-suppressor-cells-and-mast-cells-mediates-tumor-specific-immunosuppression-in-prostate-cancer
#12
Mario P Colombo, Elena Jachetti, Valeria Cancila, Alice Rigoni, Lucia Bongiovanni, Barbara Cappetti, Beatrice Belmonte, Claudia Enriquez, Patrizia Casalini, Paola Ostano, Barbara Frossi, Sabina Sangaletti, Claudia Chiodoni, Giovanna Chiorino, Carlo E Pucillo, Claudio Tripodo
Immunotherapy, including the use of checkpoint inhibitors, is a potent therapeutic approach for some cancers, but has limited success with prostate tumors, in which immune suppression is instigated by the tumor. The immunosuppressive capacity of mast cells, which promote adenocarcinoma development in the prostate, prompted our investigation on whether mast cells promote tolerance to SV40 Large-T antigen, the transforming oncogene in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. The incidence of adenocarcinoma was reduced in the offspring of a cross between TRAMP mice and mast cell-deficient KitWsh mice...
March 9, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29520448/targeting-the-tumor-microenvironment-with-immunotherapy-for-genitourinary-malignancies
#13
REVIEW
Ariel E Marciscano, Ravi A Madan
Bacillus Calmette-Guérin in urothelial carcinoma, high-dose interleukin-2 in renal cell carcinoma, and sipuleucel-T in prostate cancer serve as enduring examples that the host immune response can be harnessed to promote effective anti-tumor immunity in genitourinary malignancies. Recently, cancer immunotherapy with immune checkpoint inhibitors has transformed the prognostic landscape leading to durable responses in a subset of urothelial carcinoma and renal cell carcinoma patients with traditionally poor prognosis...
March 8, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29510739/measuring-multiple-parameters-of-cd8-tumor-infiltrating-lymphocytes-in-human-cancers-by-image-analysis
#14
Keith E Steele, Tze Heng Tan, René Korn, Karma Dacosta, Charles Brown, Michael Kuziora, Johannes Zimmermann, Brian Laffin, Moritz Widmaier, Lorenz Rognoni, Ruben Cardenes, Katrin Schneider, Anmarie Boutrin, Philip Martin, Jiping Zha, Tobias Wiestler
BACKGROUND: Immuno-oncology and cancer immunotherapies are areas of intense research. The numbers and locations of CD8+ tumor-infiltrating lymphocytes (TILs) are important measures of the immune response to cancer with prognostic, pharmacodynamic, and predictive potential. We describe the development, validation, and application of advanced image analysis methods to characterize multiple immunohistochemistry-derived CD8 parameters in clinical and nonclinical tumor tissues. METHODS: Commercial resection tumors from nine cancer types, and paired screening/on-drug biopsies of non-small-cell lung carcinoma (NSCLC) patients enrolled in a phase 1/2 clinical trial investigating the PD-L1 antibody therapy durvalumab (NCT01693562), were immunostained for CD8...
March 6, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29491468/evaluation-of-a-pretargeting-strategy-for-molecular-imaging-of-the-prostate-stem-cell-antigen-with-a-single-chain-antibody
#15
Lena Tienken, Natascha Drude, Isabell Schau, Oliver H Winz, Achim Temme, Elmar Weinhold, Felix M Mottaghy, Agnieszka Morgenroth
In pretargeted radio-immunotherapy, the gradual administration of a non-radioactive tumor antigen-addressing antibody-construct and the subsequent application of a radioactive labeled, low molecular weight substance enable a highly effective and selective targeting of tumor tissue. We evaluated this concept in prostate stem cell antigen (PSCA)-positive cancers using the antigen-specific, biotinylated single chain antibody scFv(AM1)-P-BAP conjugated with tetrameric neutravidin. To visualize the systemic biodistribution, a radiolabeled biotin was injected to interact with scFv(AM1)-P-BAP/neutravidin conjugate...
February 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29490991/targeting-tumor-vasculature-with-tnf-leads-effector-t-cells-to-the-tumor-and-enhances-therapeutic-efficacy-of-immune-checkpoint-blockers-in-combination-with-act
#16
Angela R Elia, Matteo Grioni, Veronica Basso, Flavio Curnis, Massimo Freschi, Angelo Corti, Anna Mondino, Matteo Bellone
PURPOSE: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTLs). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the tumor vasculature, and improving intra-tumor infiltration by activated CTLs, could sensitize tumors to ICB with antibodies specific for the PD-1 and CTLA-4 receptors...
February 28, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29464943/molecular-profiling-of-pooled-circulating-tumor-cells-from-prostate-cancer-patients-using-dual-antibody-functionalized-microfluidic-device
#17
Changqing Yin, Yuhui Wang, Jia Ji, Bo Cai, Hao Chen, Zhonghua Yang, Kun Wang, Changliang Luo, Wu-Wen Zhang, Chunhui Yuan, Fubing Wang
Here, we constructed a novel dual-antibody-functionalized microfluidic device by employing antibodies against PSMA and EpCAM to capture CTCs from PCa patients in order to capture multiple subpopulations of CTCs at different metastatic stages. In vitro experiments with dual capture system for capturing both LnCAP and LnCAP-EMT cells have shown significantly enhanced capture efficiency as compared to that of EpCAM single capture system. Furthermore, dual capture system could successfully identify CTCs in 20 out of 24 (83...
February 21, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29458983/first-report-of-prostate-specific-membrane-antigen-targeted-immunotherapy-in-prostate-cancer-the-future-is-bright
#18
EDITORIAL
Alastair D Lamb, Richard J Bryant, Ian G Mills, Freddie C Hamdy
No abstract text is available yet for this article.
February 16, 2018: European Urology
https://www.readbyqxmd.com/read/29434366/potentiating-prostate-cancer-immunotherapy-with-oncolytic-viruses
#19
REVIEW
Patrick Lee, Shashi Gujar
The clinical effectiveness of immunotherapies for prostate cancer remains subpar compared with that for other cancers. The goal of most immunotherapies is the activation of immune effectors, such as T cells and natural killer cells, as the presence of these activated mediators positively correlates with patient outcomes. Clinical evidence shows that prostate cancer is immunogenic, accessible to the immune system, and can be targeted by antitumour immune responses. However, owing to the detrimental effects of prostate-cancer-associated immunosuppression, even the newest immunotherapeutic approaches fail to initiate the clinically desired antitumour immune reaction...
February 13, 2018: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29421982/immune-based-therapies-for-metastatic-prostate-cancer-an-update
#20
Md Kamal Hossain, Kamrun Nahar, Osaana Donkor, Vasso Apostolopoulos
Prostate cancer (PC) is a common malignancy among elderly males and is noncurable once it becomes metastatic. In recent years, a number of antigen-delivery systems have emerged as viable and promising immunotherapeutic agents against PC. The approval of sipuleucel-T by the US FDA for the treatment of males with asymptomatic or minimally symptomatic castrate resistant PC was a landmark in cancer immunotherapy, making this the first approved immunotherapeutic. A number of vaccines are under clinical investigation, each having its own set of advantages and disadvantages...
February 1, 2018: Immunotherapy
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