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https://www.readbyqxmd.com/read/29329556/cancer-immunotherapy-beyond-immune-checkpoint-inhibitors
#1
REVIEW
Julian A Marin-Acevedo, Aixa E Soyano, Bhagirathbhai Dholaria, Keith L Knutson, Yanyan Lou
Malignant cells have the capacity to rapidly grow exponentially and spread in part by suppressing, evading, and exploiting the host immune system. Immunotherapy is a form of oncologic treatment directed towards enhancing the host immune system against cancer. In recent years, manipulation of immune checkpoints or pathways has emerged as an important and effective form of immunotherapy. Agents that target cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1 (PD-L1) are the most widely studied and recognized...
January 12, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29320954/the-value-of-fixed-rasburicase-dosing-versus-weight-based-dosing-in-the-treatment-and-prevention-of-tumor-lysis-syndrome
#2
Alyssa Boutin, Alison Blackman, David M O'Sullivan, Nicholas Forcello
Background Rasburicase is a recombinant urate oxidase enzyme used for the treatment and prevention of tumor lysis syndrome. Our objective was to assess the efficacy of indication-based, low-dose rasburicase administration compared to the Food and Drug Administration-approved weight-based dosing. Methods This was a retrospective cohort study utilizing data from a tertiary medical center including patients admitted from 2012 to 2016, who received at least one dose of rasburicase. The primary outcome was achieving a uric acid level less than 7...
January 1, 2018: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29312553/development-of-novel-target-modules-for-retargeting-of-unicar-t-cells-to-gd2-positive-tumor-cells
#3
Nicola Mitwasi, Anja Feldmann, Ralf Bergmann, Nicole Berndt, Claudia Arndt, Stefanie Koristka, Alexandra Kegler, Justyna Jureczek, Anja Hoffmann, Armin Ehninger, Marc Cartellieri, Susann Albert, Claudia Rossig, Gerhard Ehninger, Jens Pietzsch, Jörg Steinbach, Michael Bachmann
As the expression of a tumor associated antigen (TAA) is commonly not restricted to tumor cells, adoptively transferred T cells modified to express a conventional chimeric antigen receptor (CAR) might not only destroy the tumor cells but also attack target-positive healthy tissues. Furthermore, CAR T cells in patients with large tumor bulks will unpredictably proliferate and put the patients at high risk of adverse side effects including cytokine storms and tumor lysis syndrome. To overcome these problems, we previously established a modular CAR technology termed UniCAR: UniCAR T cells can repeatedly be turned on and off via dosing of a target module (TM)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305552/venetoclax-for-patients-with-chronic-lymphocytic-leukemia-who-progressed-during-or-after-idelalisib-therapy
#4
Steven Coutre, Michael Choi, Richard R Furman, Herbert Eradat, Leonard Heffner, Jeffrey A Jones, Brenda Chyla, Lang Zhou, Suresh Agarwal, Tina Waskiewicz, Maria Verdugo, Rod A Humerickhouse, Jalaja Potluri, William G Wierda, Matthew S Davids
B-cell receptor pathway inhibitors (BCRi) have transformed treatment for chronic lymphocytic leukemia (CLL); however, efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRi is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi prior to enrollment...
January 5, 2018: Blood
https://www.readbyqxmd.com/read/29298689/anti-gd2-4-1bb-chimeric-antigen-receptor-t-cell-therapy-for-the-treatment-of-chinese-melanoma-patients
#5
Jiayi Yu, Xiaowen Wu, Junya Yan, Huan Yu, Longwen Xu, Zhihong Chi, Xinan Sheng, Lu Si, Chuanliang Cui, Jie Dai, Meng Ma, Tianxiao Xu, Yan Kong, Jun Guo
BACKGROUND: Chimeric antigen receptor (CAR)-engineered T cells have demonstrated promising clinical efficacy in patients with B cell lymphoma. However, the application of CAR-T cell therapy in the treatment of other solid tumors has been limited. We incorporated 4-1BB into the anti-GD2 CAR-T cells to test their cytotoxicity in melanoma in vitro and in vivo. Moreover, we reported the expression of ganglioside GD2 in non-Caucasian melanoma populations for the first time, thus providing a basis for future clinical research...
January 3, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29296857/effects-of-daratumumab-on-natural-killer-cells-and-impact-on-clinical-outcomes-in-relapsed-or-refractory-multiple-myeloma
#6
Tineke Casneuf, Xu Steven Xu, Homer C Adams, Amy E Axel, Christopher Chiu, Imran Khan, Tahamtan Ahmadi, Xiaoyu Yan, Sagar Lonial, Torben Plesner, Henk M Lokhorst, Niels W C J van de Donk, Pamela L Clemens, A Kate Sasser
Daratumumab, a human CD38 imunoglobulin G 1κ monoclonal antibody, has demonstrated clinical activity and a manageable safety profile in monotherapy and combination therapy clinical trials in relapsed and/or refractory multiple myeloma. CD38 is expressed at high levels on myeloma cells and, to a lesser extent, on immune effector cells, including natural killer (NK) cells, which are important for daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC). Here, the pharmacodynamic effects of daratumumab monotherapy on NK cells, and the effect of NK cell dynamics on daratumumab efficacy and safety, were assessed...
October 24, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290749/rasburicase-induced-hemolytic-anemia-in-an-adolescent-with-unknown-glucose-6-phosphate-dehydrogenase-deficiency
#7
Manzilat Akande, Anthony N Audino, Joseph D Tobias
Rasburicase, used in the prevention and treatment of tumor lysis syndrome (TLS), may cause hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Although routine screening for G6PD deficiency has been recommended, given the turnaround time for test results and the urgency to treat TLS, such screening may not be feasible. We report a case of rasburicase-induced hemolytic anemia without methemoglobinemia in an adolescent with T-cell lymphoblastic lymphoma, TLS, and previously unrecognized G6PD deficiency...
November 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29284359/rare-incidence-of-tumor-lysis-syndrome-in-metastatic-prostate-cancer-following-treatment-with-docetaxel
#8
Sharonlin Bhardwaj, Seema Varma
Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29284345/from-skin-to-spontaneous-lysis-a-case-of-spontaneous-tumor-lysis-syndrome-in-metastatic-melanoma
#9
Charis G Durham, Jon Herrington, Susan Seago, Chelsea Williams, Mark H Holguin
Tumor lysis syndrome is a life-threatening complication that often occurs after administration of cytotoxic therapy, but rarely occurs spontaneously without chemotherapy. This vignette describes a 59-year-old male with known extensive metastatic melanoma who presented to the hospital with spontaneous tumor lysis syndrome. Most spontaneous tumor lysis cases occur in patients with acute leukemias and aggressive lymphomas; however, this rare case depicts a patient with melanoma developing tumor lysis before the administration of chemotherapy...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29284308/fighting-cancer-with-viruses-oncolytic-virus-therapy-in-china
#10
Ding Wei, Jing Xu, Xinyuan Liu, Zhi-Nan Chen, Huijie Bian
Oncolytic virus has the special property with selective infection of tumor cells, leading to oncolysis of cancer cells and minimal toxicity to normal tissues, which is administrated in cancer therapy called oncolytic virotherapy. As a biological agent, oncolytic virus could induce tumor cell lysis, local immunological reaction, and enhance systemic anti-tumor immunity. These immune stimulatory properties of oncolytic virus will provide enormous benefits to override cancer. Nowadays, a great variety of oncolytic viruses including genetically engineered and natural viruses have shown promise in preclinical models and clinical studies...
December 28, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29275833/efficacy-against-human-prostate-cancer-by-prostate-specific-membrane-antigen-specific-transforming-growth-factor-%C3%AE-insensitive-genetically-targeted-cd8-t-cells-derived-from-patients-with-metastatic-castrate-resistant-disease
#11
Qiang Zhang, Brian T Helfand, Benedito A Carneiro, Weijun Qin, Ximing J Yang, Chung Lee, Weipeng Zhang, Francis J Giles, Massimo Cristofanilli, Timothy M Kuzel
Current immunotherapy has limited efficacy on metastatic castrate-resistant prostate cancer (mCRPC). We therefore sought to improve the antitumor ability of mCRPC patient-derived CD8+ T-cells by the endowment of specificity to prostate-specific membrane antigen (PSMA) and insensitivity to immunosuppressant molecule transforming growth factor-β (TGF-ß) under the control of herpes simplex virus-1 thymidine kinase. CD8+ T-cells were collected by leukapheresis and cultured in a Food and Drug Administration-approved Cell Processing Work Station...
December 21, 2017: European Urology
https://www.readbyqxmd.com/read/29261479/managing-patients-with-oncologic-complications-in-the-emergency-department
#12
David Wacker, Michael T McCurdy
As the prevalence of cancer continues to increase in the general population and improvements in cancer treatment prolong survival, the incidence of patients presenting to the emergency department with oncologic complications will, similarly, continue to rise. This issue reviews 3 of the more common presentations of oncology patients to the emergency department: metastatic spinal cord compression, tumor lysis syndrome, and febrile neutropenia. Signs and symptoms of these conditions can be varied and nonspecific, and may be related to the malignancy itself or to an adverse effect of the cancer treatment...
January 2018: Emergency Medicine Practice
https://www.readbyqxmd.com/read/29230244/tumor-lysis-syndrome-in-patients-with-hematological-malignancies
#13
REVIEW
Yohannes Belay, Ketsela Yirdaw, Bamlaku Enawgaw
Tumor lysis syndrome is a metabolic complication that may follow the initiation of cancer therapy. It commonly occurs in hematological malignant patients particularly non-Hodgkin's lymphoma and acute leukemia due to chemotherapy or spontaneously. It is characterized by a biochemical abnormality such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and its clinical outcome is directly related to these biochemical abnormalities. Prevention and treatment of tumor lysis syndrome depend on immediate recognition of patients at risk...
2017: Journal of Oncology
https://www.readbyqxmd.com/read/29225880/tumor-lysis-syndrome-with-massive-hyperphosphatemia-and-hyperuricemia
#14
Abhilash Koratala
Tumor lysis syndrome (TLS) occurs when tumor cells release their contents into the bloodstream, typically in response to chemotherapy, leading to the characteristic findings of hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acute kidney injury. Twinkle artifacts on renal ultrasound may indicate calcium phosphate deposits in such patients.
December 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29225869/spontaneous-tumor-lysis-syndrome-in-colon-cancer-a-case-report-and-literature-review
#15
David Sommerhalder, Amol M Takalkar, Rodney Shackelford, Prakash Peddi
Although tumor lysis syndrome is well described, it is rarely seen or suspected in solid malignancies. Early recognition of this entity is paramount in reducing morbidity and mortality. Treating physicians should be aware of this possibility in solid tumor patients with either bulky disease or extensive liver involvement.
December 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/29222263/crisis-management-in-the-treatment-of-childhood-acute-lymphoblastic-leukemia-putting-right-what-can-go-wrong-emergency-complications-of-disease-and-treatment
#16
REVIEW
Rachael Hough, Ajay Vora
The improvement in overall survival in children with acute lymphoblastic leukemia (ALL) over the last 5 decades has been considerable, with around 90% now surviving long term. The risk of relapse has been reduced to such an extent that the risk of treatment-related mortality is now approaching that of mortality caused by relapse. Toxicities may also lead to the suboptimal delivery of chemotherapy (treatment delays, dose reductions, dose omissions), potentially increasing relapse risk, and short- and long-term morbidity, adding to the "burden of therapy" in an increasing number of survivors...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29218495/systemic-epstein-barr-virus-positive-t-cell-lymphoproliferative-disorders-of-childhood-with-fulminant-leukocytosis-and-tumor-lysis-a-case-report-with-autopsy-findings
#17
Sachie Wada, Takayuki Suzuki, Koichi Kitazume, Akira Fujita, Seiichiro Shimizu
Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (T-LPD) of childhood is an extremely rare disease characterized by an aggressive clinical course and very poor prognosis. We report an adolescent male with systemic EBV-positive T-LPD of childhood after primary EBV infection, resulting in a fatal clinical course within 9 days, along with autopsy findings. A 19-year-old male without an immunocompromised status presented with an acute onset of high fever, and was hospitalized for persistent fever, vomiting and diarrhea on the 5th day from onset...
December 7, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29208883/tumor-lysis-syndrome-and-hyperleukocytosis-in-childhood-acute-lymphoblastic-leukemia-in-a-tertiary-care-hospital
#18
R Tasmeen, A Islam, S T Alam, M Begum
Acute lymphoblastic leukemia is the most common (77%) childhood leukemia and also the most common neoplastic disease in children. Acute lymphoblastic leukemia initially present with hyperleukocytosis (WBC count more than 50,000/mm³) in twenty percent cases. These children are particularly at risk of development of tumor lysis syndrome (TLS). Tumor lysis syndrome is a metabolic disorder consists of hyperuricaemia, hyperkalemia, hyperphosphataemia, hypocalcaemia with or without renal insufficiency. It is the most common disease related emergency encountered by physicians caring for cancer of children and adult...
October 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/29203786/antigen-specific-oncolytic-mv-based-tumor-vaccines-through-presentation-of-selected-tumor-associated-antigens-on-infected-cells-or-virus-like-particles
#19
Stefan Hutzler, Stephanie Erbar, Robert A Jabulowsky, Jan R H Hanauer, Jürgen H Schnotz, Tim Beissert, Bianca S Bodmer, Regina Eberle, Klaus Boller, Thorsten Klamp, Ugur Sahin, Michael D Mühlebach
Recombinant vaccine strain-derived measles virus (MV) is clinically tested both as vaccine platform to protect against other pathogens and as oncolytic virus for tumor treatment. To investigate the potential synergism in anti-tumoral efficacy of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor antigen, claudin-6, for pre-clinical proof of concept. To enhance immunogenicity, both antigens were presented by retroviral virus-like particle produced in situ during MV-infection. All recombinant MV revealed normal growths, genetic stability, and proper expression and presentation of both antigens...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29202325/co-delivery-of-human-cancer-testis-antigens-with-adjuvant-in-protein-nanoparticles-induces-higher-cell-mediated-immune-responses
#20
Medea Neek, Jo Anne Tucker, Tae Il Kim, Nicholas M Molino, Edward L Nelson, Szu-Wen Wang
Nanoparticles have attracted considerable interest as cancer vaccine delivery vehicles for inducing sufficient CD8+ T cell-mediated immune responses to overcome the low immunogenicity of the tumor microenvironment. Our studies described here are the first to examine the effects of clinically-tested human cancer-testis (CT) peptide epitopes within a synthetic nanoparticle. Specifically, we focused on two significant clinical CT targets, the HLA-A2 restricted epitopes of NY-ESO-1 and MAGE-A3, using a viral-mimetic packaging strategy...
November 20, 2017: Biomaterials
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