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prostate cancer immunotherapy

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https://www.readbyqxmd.com/read/28644303/prostate-cancer-immunotherapy-the-path-forward
#1
Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer. RECENT FINDINGS: Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28636142/clinical-development-of-immunotherapy-for-prostate-cancer
#2
REVIEW
Masanori Noguchi, Noriko Koga, Tsukasa Igawa, Kyogo Itoh
Prostate cancer is the most common cancer in men, and the second leading cause of cancer-related death in Western countries. Prostate cancer-related death occurs in patients with metastatic castration-resistant prostate cancer. Although several new drugs for castration-resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28610671/pulmonary-manifestations-of-urothelial-carcinoma-of-the-bladder
#3
REVIEW
Abhinav Agrawal, Sonu Sahni, Abhinav K Vulisha, Rammohan Gumpeni, Rakesh Shah, Arunabh Talwar
Urothelial carcinoma (Transitional cell carcinoma) of the bladder is the pre-dominant histological type of bladder cancer in the United States and Europe. Patients with bladder cancer usually present with painless hematuria. The diagnosis is often delayed, as the symptoms are similar to various other benign conditions such as urinary tract infection, prostatitis or renal calculi. In some patients, the metastatic lesions will cause the initial presenting symptoms. We conducted a MedLine/PubMED search identifying all relevant articles with "pulmonary manifestations", "urothelial bladder cancer", "manifestations of bladder cancer" or a combination of these terms in the title...
July 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/28608115/phase-i-trial-of-antigen-targeted-autologous-dendritic-cell-based-vaccine-with-in-vivo-activation-of-inducible-cd40-for-advanced-prostate-cancer
#4
Guru Sonpavde, John D McMannis, Yu Bai, Mamatha R Seethammagari, Joan M C Bull, Victoria Hawkins, Theresa K Dancsak, Natasha Lapteva, Jonathan M Levitt, Annemarie Moseley, David M Spencer, Kevin M Slawin
This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation...
June 12, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28606732/constitutive-and-acquired-mechanisms-of-resistance-to-immune-checkpoint-blockade-in-human-cancer
#5
Matteo Bellone, Angela Rita Elia
Cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes has been revolutionizing medical oncology, and the clinical success of monoclonal antibodies targeting either cytotoxic T lymphocyte antigen-4 (CTLA-4) or program death-1 (PD-1) in patients affected by melanoma, Hodgkin's lymphoma, Merkel cell carcinoma, and head and neck, bladder, renal cell or non-small cell lung cancer is way beyond the most optimistic expectation. However, immune checkpoint blockade (ICB) has failed to arrest progression in a consistent amount of patients affected by those tumors, and various histological types, including breast, colon and prostate cancer, are less sensitive to this therapeutic approach...
June 2, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28600175/overcoming-immunosuppression-in-bone-metastases
#6
REVIEW
Zachary Z Reinstein, Sahithi Pamarthy, Vinay Sagar, Ricardo Costa, Sarki A Abdulkadir, Francis J Giles, Benedito A Carneiro
Bone metastases are present in up to 70% of advanced prostate and breast cancers and occur at significant rates in a variety of other cancers. Bone metastases can be associated with significant morbidity. The establishment of bone metastasis activates several immunosuppressive mechanisms. Hence, understanding the tumor-bone microenvironment is crucial to inform the development of novel therapies. This review describes the current standard of care for patients with bone metastatic disease and novel treatment options targeting the microenvironment...
May 12, 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28593860/evolving-adoptive-cellular-therapies-in-urological-malignancies
#7
REVIEW
Yien Ning Sophia Wong, Kroopa Joshi, Martin Pule, Karl S Peggs, Charles Swanton, Sergio A Quezada, Mark Linch
Immunotherapies have long been used to treat urological cancers but rarely lead to cure. In the past 5 years, success of immune checkpoint inhibition has led to a resurgence of enthusiasm for immunotherapy in the treatment of solid tumours. Increased understanding of tumour immune biology, technological advancements of gene transfer and cell culture, and improved clinical infrastructures for routine delivery of cell products, has made cell-based immunotherapeutics a real prospect for cancer therapy. These scientific and clinical activities, attempting to exploit the innate and adaptive immune systems for therapeutic gain, are well exemplified by the urological malignancies of renal, bladder, prostate, and penile cancer, a group of anatomically localised diseases, each with a distinct biology and different immunotherapeutic challenges...
June 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28583748/development-of-parp-inhibitors-in-gynecological-malignancies
#8
REVIEW
Yvonne L E Ang, David S P Tan
PARP inhibitors demonstrate synthetic lethality in tumors with BRCA1/2 mutations and other homologous recombination repair deficiencies by interfering with DNA repair and causing direct toxicity to DNA through PARP trapping. PARP inhibitors have been shown to be beneficial in the treatment of BRCA1/2-mutated ovarian cancers, which has led to a shift in the treatment paradigm of this disease. Further studies to establish the role of PARP inhibitors during earlier stages of treatment are ongoing. The use of PARP inhibitors in other cancers with homologous recombination repair deficiencies, such as breast cancer and prostate cancer, is gradually evolving as well, including their use in the neoadjuvant and adjuvant settings...
March 14, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28581441/nk-cell-heparanase-controls-tumor-invasion-and-immune-surveillance
#9
Eva M Putz, Alyce J Mayfosh, Kevin Kos, Deborah S Barkauskas, Kyohei Nakamura, Liam Town, Katharine J Goodall, Dean Y Yee, Ivan Kh Poon, Nikola Baschuk, Fernando Souza-Fonseca-Guimaraes, Mark D Hulett, Mark J Smyth
NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA)...
June 5, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28573914/treatment-strategies-for-dna-repair-deficient-prostate-cancer
#10
Benjamin A Teply, Emmanuel S Antonarakis
Common recurrent genetic alterations have been identified in prostate cancer through comprehensive sequencing efforts, and the prevalence of mutations in DNA repair pathway genes in patients with advanced and metastatic disease approaches 20-25%. Identification of these underlying DNA repair defects may present unique treatment opportunities for patients, both in terms of standard-of-care treatments and selected investigational agents. Areas covered: We review our current understanding of the genomic landscape of prostate cancer, with special attention to alterations in DNA repair pathway genes in metastatic castration-resistant disease...
June 12, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28561807/personalized-peptide-vaccines-and-their-relation-to-other-therapies-in-urological-cancer
#11
REVIEW
Takahiro Kimura, Shin Egawa, Hirotsugu Uemura
Immunotherapy is an important therapeutic modality for urological cancers and several immunological agents for their treatment, such as sipuleucel-T and immune checkpoint inhibitors, have been approved by the FDA. Personalized peptide vaccines (PPVs) are an immunotherapy that uses multiple cancer peptides that are selected to complement pre-existing host immunity. Vaccination with an appropriate, individualized selection of peptides, chosen from a list of candidates, induces stronger and more rapid antitumour immunity in comparison with inoculation of conventional peptide vaccines...
May 31, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28540598/parp-inhibitors-in-prostate-cancer
#12
REVIEW
Praveen Ramakrishnan Geethakumari, Matthew J Schiewer, Karen E Knudsen, Wm Kevin Kelly
The genomic landscape of metastatic prostate cancer (mPCa) reveals that up to 90% of patients harbor actionable mutations and >20% have somatic DNA repair gene defects (DRD). This provides the therapeutic rationale of PARP inhibition (PARPi) to achieve "synthetic lethality" in treating this fatal disease. Clinical trials with PARP inhibitors have shown significant response rates up to 88% for PCa patients having DRD like BRCA1/2 or ATM mutations. The FDA has awarded "breakthrough designation" to develop the PARPi olaparib in treating this subset of metastatic PCa patients...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28537896/5t4-oncofoetal-glycoprotein-an-old-target-for-a-novel-prostate-cancer-immunotherapy
#13
Federica Cappuccini, Emily Pollock, Stephen Stribbling, Adrian V S Hill, Irina Redchenko
The tumour-associated antigen 5T4 is an attractive target for cancer immunotherapy. However to date, reported 5T4-specific cellular immune responses induced by various immunisation platforms have been largely weak or non-existent. In the present study, we have evaluated a heterologous prime boost regime based on the simian adenovirus ChAdOx1 and modified vaccinia virus Ankara (MVA) expressing 5T4 for immunogenicity and tumour protective efficacy in a mouse cancer model. Vaccination-induced immune responses were strong, durable and attributable primarily to CD8+ T cells...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28534538/prostate-cancer-better-vistas-ahead-potential-and-pitfalls-of-immunotherapy
#14
Ravi A Madan, James L Gulley
No abstract text is available yet for this article.
May 23, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28533357/tlr9-expression-and-secretion-of-lif-by-prostate-cancer-cells-stimulates-accumulation-and-activity-of-polymorphonuclear-mdscs
#15
Haejung Won, Dayson Moreira, Chan Gao, Priyanka Duttagupta, Xingli Zhao, Edwin Manuel, Don Diamond, Yate-Ching Yuan, Zheng Liu, Jeremy Jones, Massimo D'Apuzzo, Sumanta Pal, Marcin Kortylewski
Proinflammatory signals promote prostate tumorigenesis and progression, but their origins and downstream effects remain unclear. We recently demonstrated that the expression of an innate immune receptor, TLR9, by prostate cancer cells is critical for their tumor-propagating potential. We investigated whether cancer cell-intrinsic TLR9 signaling alters composition of the prostate tumor microenvironment. We generated Ras/Myc (RM9) and Myc-driven (Myc-CaP) prostate cancer cells expressing the tetracycline-inducible gene Tlr9 (Tlr9(ON) ) or the control LacZ (LacZ(ON) )...
May 22, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28504251/programmable-co-delivery-of-the-immune-checkpoint-inhibitor-nlg919-and-chemotherapeutic-doxorubicin-via-a-redox-responsive-immunostimulatory-polymeric-prodrug-carrier
#16
Jing-Jing Sun, Yi-Chao Chen, Yi-Xian Huang, Wen-Chen Zhao, Yan-Hua Liu, Raman Venkataramanan, Bin-Feng Lu, Song Li
To achieve synergistic therapeutic efficacy and prevent cancer relapse, chemotherapy and immunotherapy have been combined as a new modality for tumor treatment. In this work, we designed a redox-responsive immunostimulatory polymeric prodrug carrier, PSSN10, for programmable co-delivery of an immune checkpoint inhibitor NLG919 (NLG) and a chemotherapeutic doxorubicin (DOX). NLG-containing PSSN10 prodrug polymers were self-assembled into nano-sized micelles that served as a carrier to load DOX (DOX/PSSN10 micelles)...
June 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28495513/high-hydrostatic-pressure-affects-antigenic-pool-in-tumor-cells-implication-for-dendritic-cell-based-cancer-immunotherapy
#17
Linda Urbanova, Nada Hradilova, Irena Moserova, Sarka Vosahlikova, Lenka Sadilkova, Michal Hensler, Radek Spisek, Irena Adkins
High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based active immunotherapy for prostate, lung and ovarian cancer. We showed here that HHP treatment of selected human cancer cell lines leads to a degradation of tumor antigens which depends on the magnitude of HHP applied and on the cancer cell line origin. Whereas prostate or ovarian cell lines displayed little protein antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are hardly detected in lung cancer cell line after treatment with HHP 250MPa at the same time...
May 8, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28491282/cell-growth-inhibition-and-apoptotic-effects-of-a-specific-anti-rtfscfv-antibody-on-prostate-cancer-but-not-glioblastoma-cells
#18
Foroogh Nejatollahi, Payam Bayat, Bahareh Moazen
Background: Single chain antibody (scFv) has shown interesting results in cancer immunotargeting approaches, due to its advantages over monoclonal antibodies. Regeneration and tolerance factor (RTF) is one of the most important regulators of extracellular and intracellular pH in eukaryotic cells. In this study, the inhibitory effects of a specific anti-RTF scFv were investigated and compared between three types of prostate cancer and two types of glioblastoma cells.  Methods: A phage antibody display library of scFv was used to select specific scFvs against RTF using panning process...
2017: F1000Research
https://www.readbyqxmd.com/read/28470201/erratum-effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#19
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
No abstract text is available yet for this article.
May 3, 2017: Nature
https://www.readbyqxmd.com/read/28440434/preclinical-studies-for-the-combination-of-paclitaxel-and-curcumin-in-cancer-therapy-review
#20
Yumeng Wei, Xinlin Pu, Ling Zhao
Cancer is one of the most common causes of death and remains the first in China and the second in the US. The common treatments for cancer include surgery, radiation, chemotherapy, targeted therapy and immunotherapy, while chemotherapy remains one of the most important treatments. However, the efficacy of chemotherapy is limited due to drug induced-toxicities and resistance, particularly multiple drug resistance (MDR). Therefore, discovery and development of novel therapeutic drugs and/or combination therapy are urgently needed to reduce toxicity and improve efficacy...
April 20, 2017: Oncology Reports
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