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Janet Roberts, Darren D O'Rielly, Proton Rahman
Psoriatic arthritis is an inflammatory arthritis associated with psoriasis. The IL-23/IL-17 axis is an important pathway in the development of psoriatic disease. Ustekinumab is a fully human monoclonal IgG1 antibody that binds to the p40 subunit of IL-12 and IL-23, which, in turn, inhibits downstream signaling pathways. PSUMMIT-1 and PSUMMIT-2 are two pivotal Phase III trials demonstrating global improvement in primary and secondary outcomes including inhibition of radiographic progression. Therapeutic benefit of ustekinumab for synovitis appears independent of previous disease modifying antirheumatic disease or anti-TNF exposure...
February 14, 2018: Immunotherapy
Maciej Kupczyk, Piotr Kuna
IL-5 is a key cytokine responsible for the maturation, recruitment and survival of eosinophils. The role of eosinophils in pathomechanisms of severe asthma and association of those cells with frequent exacerbations are well accepted. Novel biologic agents including anti-IL-5 antibodies (mepolizumab and reslizumab) as well as anti-IL-5 receptor α chain (benralizumab) have been developed. Benralizumab (Fasenra™) leads to reduced eosinophil counts in airway mucosa, blood, sputum and a clear inhibition of eosinophil differentiation and maturation in the bone marrow...
January 23, 2018: Immunotherapy
Madan Jagasia, Robert Zeiser, Michael Arbushites, Patricia Delaite, Brian Gadbaw, Nikolas von Bubnoff
For patients with hematologic malignancies and disorders, allogeneic hematopoietic stem cell transplantation offers a potentially curative treatment option. Many patients develop graft-versus-host disease (GVHD), a serious complication and leading cause of nonrelapse mortality. Corticosteroids are the standard first-line treatment for GVHD; however, patients often become steroid-refractory or remain corticosteroid-dependent. New second-line treatment options are needed to improve patient outcomes. Here we review the role of JAK1 and JAK2 in acute and chronic GVHD...
January 10, 2018: Immunotherapy
Chungyong Han, Byoung S Kwon
Chimeric antigen receptor (CAR) T cells have outstanding therapeutic potential for treating blood cancers. The prospects for this technology have accelerated basic research, clinical translation and Big Pharma's investment in the field of T-cell therapeutics. This interest has led to the discovery of key factors that affect CAR T-cell efficacy and play pivotal roles in T-cell immunology. Herein, we introduce advances in adoptive immunotherapy and the birth of CAR T cells, and review CAR T-cell studies that focus on three important features: CAR constructs, target antigens and T-cell phenotypes...
March 2018: Immunotherapy
Beom K Choi, Seon-Hee Kim, Young H Kim, Byoung S Kwon
Studies over the last 30 years have shown the promise of cancer immunotherapy using T cells. In particular, since the report by Rosenberg and colleagues in 2002 that adoptive T-cell therapy (ACT) under lymphopenic conditions substantially increased response rates in melanoma patients, ACT has become a promising immunotherapeutic route to cancer treatment. Here we provide a brief history of ACT and review the characteristics of T-cell therapeutics that are specific to this approach. Since every T-cell treatment has its own unique properties in terms of number and type of target antigens, and number of epitopes and type of T cells, we review the main strategies for designing ACT: how Ag specificity is determined, how is it standardized and the need for lymphodepletion to induce epitope spreading...
March 2018: Immunotherapy
Sarah K Lane-Reticker, Robert T Manguso, W Nicholas Haining
No abstract text is available yet for this article.
March 2018: Immunotherapy
Khalil Saleh, Nadine Khalifeh-Saleh, Hampig Raphaël Kourie, Fadi Nasr, Georges Chahine
No abstract text is available yet for this article.
March 2018: Immunotherapy
Thiru Prasanna, Catriona M McNeil, Theresa Nielsen, David Parkin
We report a case of isolated immune-related pancreatic exocrine insufficiency in a patient treated with pembrolizumab for metastatic melanoma. This patient presented with explosive diarrhea and was treated with high dose corticosteroids for possible immune-related colitis. However, biopsies from colon and duodenum did not show any histological evidence of colitis/enteritis. Serum amylase and lipase were not elevated. There was no evidence of pancreatitis or pancreatic metastases on imaging. Significantly lower fecal elastase test on two occasions confirmed the diagnosis of pancreatic exocrine insufficiency...
March 2018: Immunotherapy
Nafiseh Pakravan, Zuhair Mohammad Hassan
Regulatory T cells (Tregs) profoundly affect tumor microenvironment and exert dominant suppression over antitumor immunity in response to self-antigen expressed by tumor. Immunotherapy targeting Tregs lead to a significant improvement in antitumor immunity. Intradermal injection of tumor antigen results in negative delayed-type hypersensitivity (DTH) type IV. However, anti-Tregs treatment/use of adjuvant along with tumor antigens turns DTH to positive. Considering Tregs as the earliest tumor sensor/responders, tumor can be regarded as Treg-mediated type IV hypersensitivity and negative DTH to tumor antigen is due to anti-inflammatory action of Tregs to tumor antigens at the injection site...
March 2018: Immunotherapy
Barbara Ziffels, Francesca Pretto, Dario Neri
AIM: The combination of tumor-targeting IL2- and TNF-based antibody-cytokine fusions has exhibited encouraging results in mouse and men. Here, we studied their combination to assess efficacy and mechanism of action in four different immunocompetent mouse models of cancer. METHODS: Mice receiving a single intratumoral injection of F8-IL2, F8-TNF or the combination were investigated for tumor-infiltrating leukocytes and rechallenged when cured. RESULTS: In three models, a proportion of treated animals could be cured, most probably by infiltrating NK and CD8+ T cells...
March 2018: Immunotherapy
Adam G Laing, Yanira Riffo-Vasquez, Ehsan Sharif-Paghaleh, Giovanna Lombardi, Paul T Sharpe
Mesenchymal stem cells (MSCs) show considerable promise as a cellular immunotherapy for the treatment of a number of autoimmune and inflammatory disorders. However, the precise physiologically and therapeutically relevant mechanism(s) by which MSCs mediate immune modulation remains elusive. Dental pulp stem cells are a readily available source of MSCs that have been reported to show similar immune modulation in vitro as bone marrow MSCs. To test their potential in vivo, we used a clinically relevant humanized mouse model of GvHD in which only human T cells engraft...
March 2018: Immunotherapy
Ru Tang, Yujia Zhai, Lili Dong, Tejsu Malla, Kai Hu
AIM: The aim of this study is to investigate the effects of constructed dendritic cell (DC)-based DNA vaccine (pRSC-NLDC145.gD-IL21) carried by chitosan nanoparticle in preventing primary or recurrent herpes simplex virus keratitis (HSK) in mice. METHODS: The expression of constructed plasmid 'pRSC-NLDC145.gD-IL21' was verified by western blot and immunofluorescence. Plasmids that were embedded in chitosan were inoculated to test its therapeutic effect against primary or recurrent HSK in mice...
March 2018: Immunotherapy
Neha Kamran, Mahmoud S Alghamri, Felipe J Nunez, Diana Shah, Antonela S Asad, Marianela Candolfi, David Altshuler, Pedro R Lowenstein, Maria G Castro
There is a large unmet need for effective therapeutic approaches for glioma, the most malignant brain tumor. Clinical and preclinical studies have enormously expanded our knowledge about the molecular aspects of this deadly disease and its interaction with the host immune system. In this review we highlight the wide array of immunotherapeutic interventions that are currently being tested in glioma patients. Given the molecular heterogeneity, tumor immunoediting and the profound immunosuppression that characterize glioma, it has become clear that combinatorial approaches targeting multiple pathways tailored to the genetic signature of the tumor will be required in order to achieve optimal therapeutic efficacy...
February 1, 2018: Immunotherapy
Atif Sohail, Adeela Mushtaq, Ahmad Iftikhar, Zabih Warraich, Sandra E Kurtin, Pavan Tenneti, Ali McBride, Faiz Anwer
We reviewed emerging immune strategies for multiple myeloma (MM) therapy excluding US FDA approved drugs. In relapsed refractory MM, isatuximab (anti-CD38) monotherapy achieved overall response (OR) of 24%. Other monoclonal antibodies that have shown efficacy in combination therapy include siltuximab (OR: 66%), indatuximab (OR: 78%), isatuximab (OR: 64.5%), pembrolizumab (OR: 60%), bevacizumab (OR: 70%), dacetuzumab (OR: 39%) and lorvotuzumab (OR: 56.4%). No OR was observed with monotherapy using BI-505, siltuximab, bevacizumab, AVE-1642, figitumumab, atacicept, milatuzumab, dacetuzumab, lucatumumab, IPH2101, lorvotuzumab, BT062 and nivolumab...
February 1, 2018: Immunotherapy
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
Ho Liam Pock, Teo Yi Wei Bryan, Tan Puay Hoon, Jabed Iqbal, Linn Yeh Ching, Goh Yeow Tee, Tan Kar Wai, Toh Han Chong, Ong Kong Wee, Yeoh Kheng Wei
AIM: The new radioimmunotherapeutic regime GAP15R aims to stimulate glucocorticoid-induced TNF-related protein (G) to overcome Treg suppression; add IFN-α (A) to promote inflammatory milieu; block PD1 (P) to disinhibit T effector cytotoxicity; add IL-15 (15) to enhance danger signals & T-cell expansion; and apply radiation (R) at critical time point to sustain localized inflammation. Patients & methods/materials & methods: This was tested in a murine 4T1 metastatic breast carcinoma model given GAP15R with regular monitoring of tumor volume and complications...
February 1, 2018: Immunotherapy
Kevin A Hay, Cameron J Turtle
No abstract text is available yet for this article.
February 1, 2018: Immunotherapy
Maureen L Aliru, Jonathan E Schoenhals, Bhanu P Venkatesulu, Clark C Anderson, Hampartsoum B Barsoumian, Ahmed I Younes, Lakshmi S K Mahadevan, Melinda Soeung, Kathryn E Aziz, James W Welsh, Sunil Krishnan
Radiotherapy is a component of the standard of care for many patients with locally advanced nonmetastatic tumors and increasingly those with oligometastatic tumors. Despite encouraging advances in local control and progression-free and overall survival outcomes, continued manifestation of tumor progression or recurrence leaves room for improvement in therapeutic efficacy. Novel combinations of radiation with immunotherapy have shown promise in improving outcomes and reducing recurrences by overcoming tumor immune tolerance and evasion mechanisms via boosting the immune system's ability to recognize and eradicate tumor cells...
February 1, 2018: Immunotherapy
Elie El Rassy, Fadi El Karak, Marwan Ghosn
No abstract text is available yet for this article.
February 1, 2018: Immunotherapy
Elahe Motevaseli, Mohammad Reza Khorramizadeh, Jamshid Hadjati, Samad Farashi Bonab, Solat Eslami, Soudeh Ghafouri-Fard
AIM: To evaluate the effect of intraperitoneal injections of heat-killed Lactobacillus crispatus on breast tumor size and overall survival of Balb/c mouse received 4T1 mammary carcinoma. Materials and methods: Different doses of L. crispatus have been injected intraperitoneally in BALB/c mice. RESULTS: Tumor size was decreased in the experiment group treated with 1 × 108 bacteria/200 μl. Treatment with 1 × 108 bacteria/200 μl resulted in survival improvement...
February 2018: Immunotherapy
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