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Pembrolizumab and bladder

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https://www.readbyqxmd.com/read/29157296/biomarkers-for-immunotherapy-in-bladder-cancer-a-moving-target
#1
REVIEW
David H Aggen, Charles G Drake
Treatment options for metastatic urothelial carcinoma (mUC) remained relative unchanged over the last 30 years with combination chemotherapy as the mainstay of treatment. Within the last year the landscape for mUC has seismically shifted following the approval of five therapies targeting the programmed cell death protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis. Notably, the anti-PD-1 antibody pembrolizumab demonstrated improved OS relative to chemotherapy in a randomized phase III study for second line treatment of mUC; this level 1 evidence led to approval from the U...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29146734/humanized-mice-in-studying-efficacy-and-mechanisms-of-pd-1-targeted-cancer-immunotherapy
#2
Minan Wang, Li-Chin Yao, Mingshan Cheng, Danying Cai, Jan Martinek, Chong-Xian Pan, Wei Shi, Ai-Hong Ma, Ralph W De Vere White, Susan Airhart, Edison T Liu, Jacques Banchereau, Michael A Brehm, Dale L Greiner, Leonard D Shultz, Karolina Palucka, James G Keck
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, non-obese diabetic (NOD).Cg-Prkdc(scid)IL2rg(tm1Wjl) /Sz (null; NSG) mice were transplanted with human (h)CD34(+) hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; nonsmall cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX)...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29069302/mechanistic-overview-of-immune-checkpoints-to-support-the-rational-design-of-their-combinations-in-cancer-immunotherapy
#3
A Rotte, J Y Jin, V Lemaire
Checkpoint receptor blockers, known to act by blocking the pathways that inhibit immune cell activation and stimulate immune responses against tumor cells, have been immensely successful in the treatment of cancer. Among several checkpoint receptors of immune cells, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), T-cell immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin-3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) are the most commonly targeted checkpoints for cancer immunotherapy...
October 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28982752/urothelial-carcinoma-of-the-bladder-and-the-rise-of-immunotherapy
#4
REVIEW
David D Chism
With the advent of platinum-based chemotherapy, survival rates for metastatic urothelial carcinoma have plateaued, giving way to the modern immunotherapy paradigm. Although immunotherapy as an effective treatment dates back to the live, attenuated bacillus Calmette-Guérin vaccine, the recent impact of immune checkpoint inhibitors targeting programmed death/programmed death-ligand 1 (PD-1/PD-L1) coupled with the promise of both anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies and indoleamine-2, 3-dioxygenase-1 (IDO-1) inhibitors have provided a resurgence...
October 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28982750/bladder-cancer-version-5-2017-nccn-clinical-practice-guidelines-in-oncology
#5
Philippe E Spiess, Neeraj Agarwal, Rick Bangs, Stephen A Boorjian, Mark K Buyyounouski, Peter E Clark, Tracy M Downs, Jason A Efstathiou, Thomas W Flaig, Terence Friedlander, Richard E Greenberg, Khurshid A Guru, Noah Hahn, Harry W Herr, Christopher Hoimes, Brant A Inman, Masahito Jimbo, A Karim Kader, Subodh M Lele, Joshua J Meeks, Jeff Michalski, Jeffrey S Montgomery, Lance C Pagliaro, Sumanta K Pal, Anthony Patterson, Elizabeth R Plimack, Kamal S Pohar, Michael P Porter, Mark A Preston, Wade J Sexton, Arlene O Siefker-Radtke, Guru Sonpavde, Jonathan Tward, Geoffrey Wile, Mary A Dwyer, Lisa A Gurski
This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up...
October 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28883282/development-of-immune-checkpoint-inhibitors
#6
Shigehisa Kitano
Immune checkpoint inhibitors are the most striking innovation in the clinical development of immunotherapy. Monoclonal antibodies (mAbs) restore and augment the antitumor immune activities of cytotoxic T cells by mainly blocking immune checkpoint molecules on T cells or their ligands on antigen-presenting and tumor cells. Based on preclinical data, many clinical trials have demonstrated the acceptable safety profiles and efficacies of mAb in various cancers. The A first-in-class approved immune checkpoint inhibitor is ipilimumab, which is a fully humanized mAb that blocks the immunosuppressive signal by cytotoxic T-lymphocyte antigen 4...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28877075/microsatellite-instability-a-predictive-biomarker-for-cancer-immunotherapy
#7
Liisa Chang, Minna Chang, Hanna M Chang, Fuju Chang
Immunotherapy has shown promising results in various types of cancers. Checkpoint inhibitor drugs developed for cancer immunotherapy have been approved by the US Food and Drug Administration (FDA) for patients with advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin lymphoma. In the latest announcement, the FDA has granted accelerated approval to pembrolizumab for pediatric and adult patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient solid tumors...
September 4, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28864844/checkpoint-inhibitors-the-new-treatment-paradigm-for-urothelial-bladder-cancer
#8
REVIEW
Heather Katz, Emnet Wassie, Mohamed Alsharedi
Bladder cancer is the most common malignancy involving the genitourinary system (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). In the USA, it is the fifth most common cancer and approximately 79,000 new cases will be diagnosed in 2017 (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). The mortality from bladder cancer is approximately 17,000 deaths each year (Siegel et al. in CA Cancer J Clin, 66:7-30, 2016). The incidence rate for bladder cancer is higher in men compared to women. Risk factors are predominantly related to tobacco smoking, although infection with Schistosoma haematobium is another risk factor in selected populations (Antoni et al...
September 1, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28749907/immunotherapy-in-urothelial-cancer-part-1-t-cell-checkpoint-inhibition-in-advanced-or-metastatic-disease
#9
Steven S Yu, Tanya B Dorff, Leslie K Ballas, Sarmad Sadeghi, Eila C Skinner, David I Quinn
Cancer of the urothelium is the sixth most common cancer in the United States and is seen predominantly in men. Most cases of this disease present as non-muscle-invasive bladder cancer (NMIBC), with cancer recurrence or progression to muscle-invasive cancer in more than 50% of patients after initial therapy. NMIBC is an immune-responsive disease, as indicated by the use of intravesical bacillus Calmette-Guérin as treatment for more than 3 decades. More recently, immunotherapy has seen much progress in a variety of cancers, including advanced and metastatic bladder cancer, in which historical 5-year survival rates are approximately 15%...
June 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28493171/immunotherapy-in-urothelial-cancer-recent-results-and-future-perspectives
#10
REVIEW
Matthew S Farina, Kevin T Lundgren, Joaquim Bellmunt
Cytotoxic chemotherapy has been the only systemic treatment of locally advanced and metastatic urothelial carcinoma for decades. Long-term survival remains stagnant around 12-14 months for patients with advanced disease who have progressed on or recurred after receiving first-line platinum-based chemotherapy. Improving clinical outcomes for patients with urothelial carcinoma in all disease settings requires the development of novel treatments, especially for patients who failed on first-line chemotherapy. Since the discovery of intravesical Bacillus-Calmette Guerin (BCG) in the 1970s for non-muscle invasive disease, there have not been any major breakthrough drugs that exploit the immune-sensitivity of bladder cancer until recently...
July 2017: Drugs
https://www.readbyqxmd.com/read/28288994/immunotherapy-beats-chemo-for-bladder-cancer
#11
(no author information available yet)
Patients with advanced urothelial carcinoma live 3 months longer, on average, when given pembrolizumab as a second-line treatment instead of chemotherapy. The finding is based on data from the first phase III trial to test an immunotherapeutic in these patients, which could lead to another label indication for the PD-1 inhibitor.
March 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28266514/bladder-cancer-pembrolizumab-is-superior-to-chemotherapy
#12
Peter Sidaway
No abstract text is available yet for this article.
May 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28214651/a-review-on-the-evolution-of-pd-1-pd-l1-immunotherapy-for-bladder-cancer-the-future-is-now
#13
REVIEW
Joaquin Bellmunt, Thomas Powles, Nicholas J Vogelzang
The treatment of bladder cancer has evolved over time to encompass not only the traditional modalities of chemotherapy and surgery, but has been particularly impacted by the use of immunotherapy. The first immunotherapy was the live, attenuated bacterial Bacillus Calmette-Guérin vaccine, which has been the standard of care non-muscle-invasive bladder cancer since 1990. Modern immunotherapy has focused on inhibitors of checkpoint proteins, which are molecules that impede immune function, thereby allowing tumor cells to grow and proliferate unregulated...
March 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28143711/response-to-pembrolizumab-in-a-patient-with-chemotherapy-refractory-bladder-cancer-with-small-cell-variant-histology-a-case-report-and-review-of-the-literature
#14
Lindsay Wilde, Siraj M Ali, Charalambos C Solomides, Jeffrey S Ross, Edouard Trabulsi, Jean Hoffman-Censits
No abstract text is available yet for this article.
December 22, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27229745/cancer-treatment-with-anti-pd-1-pd-l1-agents-is-pd-l1-expression-a-biomarker-for-patient-selection
#15
REVIEW
Lucia Festino, Gerardo Botti, Paul Lorigan, Giuseppe V Masucci, Jason D Hipp, Christine E Horak, Ignacio Melero, Paolo A Ascierto
Strategies to help improve the efficacy of the immune system against cancer represent an important innovation, with recent attention having focused on anti-programmed death (PD)-1/PD-ligand 1 (L1) monoclonal antibodies. Clinical trials have shown objective clinical activity of these agents (e.g., nivolumab, pembrolizumab) in several malignancies, including melanoma, non-small-cell lung cancer, bladder cancer, squamous head and neck cancer, renal cell cancer, ovarian cancer, microsatellite-unstable colorectal cancer, and Hodgkin's lymphoma...
June 2016: Drugs
https://www.readbyqxmd.com/read/26864062/-immune-checkpoint%C3%A2-targeted-cancer-immunotherapies
#16
REVIEW
Julian Swatler, Ewa Kozłowska
Tumor cells may express on their surface various characteristic antigens that can induce antitumor immunity. However, cancer in human body may induce an immunosuppressive microenvironment that limits immune response to its antigens. For many years scientists have tried to develop an immunotherapy which would induce a potent antitumor immune response and lead to an elimination of the disease. One of the most promising immunotherapies is blockade of immune checkpoints, i.e. a group of costimulatory molecules negatively regulating the immune system...
January 26, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/26063384/the-immunocheckpoints-in-modern-oncology-the-next-15-years
#17
EDITORIAL
Francesco Massari, Matteo Santoni, Chiara Ciccarese, Daniele Santini
The notion that the immune system can act as a key factor in controlling cancer cell proliferation and thus its stimulation may be an important resource for cancer therapy has long been known. Tumors can elude the immune system by deploying proteins that shut down the immune response by binding to specific surface receptors on immune cells. Several promising strategies have been designed to overcome cancer cells' ability to suppress the immune surveillance. Immune checkpoint molecules that block cytotoxic T-lymphocyte associated antigen-4 (ipilimumab) or the programmed death-1/programmed death-ligand 1 axis (i...
July 2015: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/26047524/pd-1-pd-l1-inhibitors
#18
REVIEW
Joel Sunshine, Janis M Taube
Tumors may adopt normal physiologic checkpoints for immunomodulation leading to an imbalance between tumor growth and host surveillance. Antibodies targeting the PD-1/PD-L1 checkpoint have shown dynamic and durable tumor regressions, suggesting a rebalancing of the host-tumor interaction. Nivolumab and pembrolizumab are the anti-PD-1 antibodies that are currently the furthest in clinical development, and anti-PD-L1 agents under investigation include MPDL3280A, MEDI4736, and BMS-936559. These agents have been used to treat advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin lymphoma, amongst other tumor types...
August 2015: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/25856776/anti-programmed-cell-death-protein-1-ligand-1-therapy-in-different-cancers
#19
REVIEW
B Homet Moreno, A Ribas
Immunologic checkpoint blockade with antibodies against the programmed cell death protein-1 (PD-1) or its ligand (PD-L1) is an effective method for reversing cancer immunosuppression and thereby promoting immune responses against several cancer types. Anti-PD-1 and anti-PD-L1 antibodies have resulted in long-term responses with minimal side effects in significant numbers of patients with melanoma, lung, kidney, bladder and triple-negative breast cancer, as well as in chemotherapy-refractory Hodgkin disease...
April 28, 2015: British Journal of Cancer
https://www.readbyqxmd.com/read/25823918/the-next-immune-checkpoint-inhibitors-pd-1-pd-l1-blockade-in-melanoma
#20
REVIEW
Kathleen M Mahoney, Gordon J Freeman, David F McDermott
PURPOSE: Blocking the interaction between the programmed cell death (PD)-1 protein and one of its ligands, PD-L1, has been reported to have impressive antitumor responses. Therapeutics targeting this pathway are currently in clinical trials. Pembrolizumab and nivolumab are the first of this anti-PD-1 pathway family of checkpoint inhibitors to gain accelerated approval from the US Food and Drug Administration (FDA) for the treatment of ipilimumab-refractory melanoma. Nivolumab has been associated with improved overall survival compared with dacarbazine in patients with previously untreated wild-type serine/threonine-protein kinase B-raf proto-oncogene BRAF melanoma...
April 1, 2015: Clinical Therapeutics
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