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Journal of Immunotherapy

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https://www.readbyqxmd.com/read/28719552/immune-checkpoint-inhibitors-in-organ-transplant-patients
#1
Adam S Kittai, Hayden Oldham, Jeremy Cetnar, Matthew Taylor
Modulation of T-cell activity through blockade of coinhibitory molecules has revolutionized the treatment of various malignancies. Several immune checkpoint inhibitors are currently Food and Drug Administration approved which target various coinhibitory pathways including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 receptor (PD-1), and programmed cell death ligand-1. Clinical trials that lead to the Food and Drug Administration approval of these agents often excluded patients with an organ transplant...
July 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28622272/nk-cell-derived-exosomes-from-nk-cells-previously-exposed-to-neuroblastoma-cells-augment-the-antitumor-activity-of-cytokine-activated-nk-cells
#2
Alireza Shoae-Hassani, Amir Ali Hamidieh, Maryam Behfar, Rashin Mohseni, Seyed A Mortazavi-Tabatabaei, Shahab Asgharzadeh
Immune cell-derived exosomes can increase immunity against tumors. In contrast, tumor-derived exosomes can reduce the immunity and can change the tumor microenvironment to further develop and provide metastasis. These effects take place by an alteration in the innate and adaptive immune cell functions. In this experiment, we studied the natural killer (NK) cells' effectiveness on tumor cells after expansion and thereafter incubated it with exosomes. The exosomes were derived from 2 populations of NK cells: (1) naive NK cells and, (2) NK cells previously exposed to neuroblastoma (NB) cells...
June 15, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28614096/two-cases-of-sinusitis-induced-by-immune-checkpoint-inhibition
#3
Eric Dein, William Sharfman, Jean Kim, Fouad Gellad, Ami A Shah, Clifton O Bingham, Laura C Cappelli
We report the acute onset of aseptic sinusitis in 2 patients receiving the immune checkpoint inhibitors, ipilimumab and nivolumab, for treatment of metastatic melanoma. Ipilimumab, a monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4, and nivolumab, targeting programmed cell death-1, have been associated with numerous immune-related adverse events. To the authors' knowledge, this is the first report of aseptic sinusitis as a consequence of immune checkpoint inhibition therapy.
June 13, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28604556/immunologic-response-elicited-in-breast-cancer-patients-receiving-a-neugcgm3-based-vaccine-as-adjuvant-therapy
#4
Anet Valdes-Zayas, Zuyen Gonzalez, Vladimir Mulens, Aliz M Vega, Kirenia Perez, Patricia Lorenzo-Luaces, Maria C Rubio, Anabely Estevez, Idelmis Curbelo, Luis E Fernandez, Tania Crombet, Zaima Mazorra
This study aimed to investigate the immunogenicity of a cancer vaccine consisting of the NeuGcGM3 ganglioside combined with the outer membrane protein complex of Neisseria meningitides to form very small size particles. The vaccine is administered together with Montanide ISA51, as adjuvant treatment for breast cancer patients. After surgical resection and standard first-line chemo/radiotherapy, breast cancer patients in stage II-III were enrolled in a phase III clinical trial and allocated into 2 strata, according to the number of positive lymph nodes [stratum I (0-3); stratum II (≥4)]...
June 9, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28604555/immune-related-neurological-symptoms-in-an-adolescent-patient-receiving-the-checkpoint-inhibitor-nivolumab
#5
Dmitry Tchapyjnikov, Alexandra J Borst
Immune checkpoint inhibitors are a novel group of immunotherapeutic agents for the treatment of cancer. Immune-related adverse events, including neurological symptoms, have been associated with these agents. We present the case of an adolescent with refractory Hodgkin lymphoma treated with nivolumab, a PD1 inhibitor, who developed Hashimoto thyroiditis, posterior reversible encephalopathy syndrome causing seizures, as well as urinary retention, truncal/appendicular spasticity, dysphagia, and a progressive encephalopathy that was clinically consistent with a diagnosis of progressive encephalopathy with rigidity and myoclonus, a stiff-person-syndrome spectrum disorder...
June 9, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28604554/severe-ocular-myositis-after-ipilimumab-treatment-for-melanoma-a-report-of-2-cases
#6
Anna Pushkarevskaya, Ulf Neuberger, Antonia Dimitrakopoulou-Strauss, Alexander Enk, Jessica C Hassel
Ipilimumab binds and blocks cytotoxic T-lymphocyte-associated antigen-4, causing enhanced T-cell reaction, antitumor response, and significant improvement of the overall survival of patients with metastatic melanoma. Patients treated with ipilimumab can develop immune-related adverse effects, primarily dermatitis, colitis, hepatitis, and hypophysitis. Although, in phase I-III studies, 64.2% of all patients suffered from immune-related adverse effects, ocular adverse effects occurred in 1.3% only. In the cases reported below, 2 patients with metastatic melanoma developed severe ocular myositis after treatment with ipilimumab...
June 9, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28604557/antigen-presentation-by-individually-transferred-hla-class-i-genes-in-hla-a-hla-b-hla-c-null-human-cell-line-generated-using-the-multiplex-crispr-cas9-system
#7
Cheol-Hwa Hong, Hyun-Jung Sohn, Hyun-Joo Lee, Hyun-Il Cho, Tai-Gyu Kim
Human leukocyte antigens (HLAs) are essential immune molecules that affect transplantation and adoptive immunotherapy. When hematopoietic stem cells or organs are transplanted with HLA-mismatched recipients, graft-versus-host disease or graft rejection can be induced by allogeneic immune responses. The function of each HLA allele has been studied using HLA-deficient cells generated from mutant cell lines or by RNA interference, zinc finger nuclease, and the CRISPR/Cas9 system. To improve HLA gene editing, we attempted to generate an HLA class I null cell line using the multiplex CRISPR/Cas9 system by targeting exons 2 and 3 of HLA-A, HLA-B, and HLA-C genes simultaneously...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28557814/significance-of-frequencies-compositions-and-or-antileukemic-activity-of-dc-stimulated-invariant-nkt-nk-and-cik-cells-on-the-outcome-of-patients-with-aml-all-and-cll
#8
Corinna L Boeck, Daniel C Amberger, Fatemeh Doraneh-Gard, Wishnu Sutanto, Thomas Guenther, Joerg Schmohl, Friedhelm Schuster, Helmut Salih, Florian Babor, Arndt Borkhardt, Helga Schmetzer
Invariant natural killer T (iNKT)/natural killer (NK)/cytokine-induced killer (CIK) cells are important for immune surveillance. (I) Novel combinations of antibody 6B11 (targeting the Vα24-Jα18-invariant T-cell receptor) with CD4/CD8/CD1d/Vα24 for iNKT subset detection and "T/NK cell-like"-iNKT subsets were defined. Compared with healthy peripheral blood mononuclear cells (MNC) (significantly) lower proportions of iNKT cells (6B11/6B11CD3/6B11CD161), NK cells (CD3CD56/CD3CD161), and CIK cells (CD3CD56/CD3CD161) were found in peripheral blood MNC from acute myeloid (AML)/acute myeloid, lymphoid (ALL)/chronic lymphoid leukemia (CLL) patients in acute disease stages...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28557813/diabetic-ketoacidosis-as-an-immune-related-adverse-event-from-pembrolizumab-in-non-small-cell-lung-cancer
#9
Giulia C Leonardi, Geoffrey R Oxnard, Andrea Haas, Joshua P Lang, Jonathan S Williams, Mark M Awad
Programmed cell death protein 1 pathway inhibitors are now routinely administered to patients with non-small cell lung cancer, and prompt recognition of immune-related adverse events is critical to managing serious drug toxicities. Here, we describe a 66-year-old man with no known history of diabetes who presented with diabetic ketoacidosis after receiving 3 doses of pembrolizumab for lung adenocarcinoma. Autoimmune diabetes is a rare but potentially life-threatening complication of programmed cell death protein 1 inhibitors...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28498142/inflammatory-myopathy-and-axonal-neuropathy-in-a-patient-with-melanoma-following-pembrolizumab-treatment
#10
Panagiotis T Diamantopoulos, Katerina Tsatsou, Olga Benopoulou, Amalia Anastasopoulou, Helen Gogas
Immune-mediated adverse effects of immune checkpoint inhibitors are rather common, but neuromyopathic immune-related adverse events are very rare. In this report, we present a unique case of a patient with a complex neuromyopathic syndrome with axonal neuropathy and inflammatory myopathy after a single dose of pembrolizumab. An 82-year-old patient with a previously untreated stage IIIc melanoma developed ptosis in the left eye, generalized weakness, and neck and shoulder pain 15 days after pembrolizumab administration...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28486273/zebularine-treatment-induces-mage-a11-expression-and-improves-ctl-cytotoxicity-using-a-novel-identified-hla-a2-restricted-mage-a11-peptide
#11
Jiandong Zhang, Meixiang Sang, Lina Gu, Fei Liu, Weijing Li, Danjing Yin, Yunyan Wu, Shina Liu, Weina Huang, Baoen Shan
Melanoma-associated antigen-A11 (MAGE-A11) is frequently expressed in breast cancer and is associated with poor prognosis. Therefore, MAGE-A11 is a potential immunotherapy target in breast cancer. MAGE-A11 expression, however, is downregulated in many patients, thus constraining the application of immunotherapy. The induction of MAGE-A11 expression is crucial for the recognition and killing of breast cancer cells by cytotoxic T lymphocytes (CTL). In this study, a series of HLA-A2-restricted candidate MAGE-A11 peptides were predicted, synthesized, and tested...
July 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28452850/sunitinib-induces-nk-%C3%AE%C2%BAb-dependent-nkg2d-ligand-expression-in-nasopharyngeal-carcinoma-and-hepatoma-cells
#12
Yu-Xian Huang, Xin-Tong Chen, Kun-Yuan Guo, Yu-Hua Li, Bing-Yi Wu, Chao-Yang Song, Yan-Jie He
Multitargeted tyrosine kinase inhibitors (MTKIs) have been shown to combine with natural killer (NK) cell adoptive transfer for the treatment in various cancers. MTKIs sensitize cancer cells to NK cell therapy through upregulation of nature killer group 2 member D ligands (NKG2DLs) on tumor cells. However, the molecular mechanism of MTKIs-mediated upregulation of NKG2DLs is still unknown. In this study, we confirmed sunitinib induced downregulation of its targets, such as vascular endothelial growth factor, platelet-derived growth factor, and c-kit in multiple-drug-resistant nasopharyngeal carcinoma cell line CNE2/DDP and hepatoma cell line HepG2...
June 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28452849/ipilimumab-induced-guillain-barr%C3%A3-syndrome-presenting-as-dysautonomia-an-unusual-presentation-of-a-rare-complication-of-immunotherapy
#13
W Kelly Wu, Kristy K Broman, Evan R Brownie, Rondi M Kauffmann
Immune-related adverse events are common and well-documented in patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 monoclonal antibody approved for the treatment of metastatic and stage III melanoma. Neurological complications are rare, but widely variable and potentially devastating. Here, we discuss a case of a patient who was treated with a single dose of ipilimumab for resected stage III melanoma. She subsequently developed pandysautonomia that manifested as a tonically dilated pupil, gastrointestinal dysmotility, urinary retention, and profound orthostatic hypotension...
June 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28441264/cd19-isoforms-enabling-resistance-to-cart-19-immunotherapy-are-expressed-in-b-all-patients-at-initial-diagnosis
#14
Jeannette Fischer, Claudia Paret, Khalifa El Malki, Francesca Alt, Arthur Wingerter, Marie A Neu, Bettina Kron, Alexandra Russo, Nadine Lehmann, Lea Roth, Eva-M Fehr, Sebastian Attig, Alexander Hohberger, Thomas Kindler, Jörg Faber
B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer and the prognosis of children with relapsed or therapy refractory disease remains a challenge. Treatment with chimeric antigen receptor-modified T cells targeting the CD19 antigen (CART-19 therapy) has been presented as a promising approach toward improving the outcome of relapsed or refractory disease. However, 10%-20% of the patients suffer another relapse. Epitope-loss under therapy pressure has been suggested as a mechanism of tumor cells to escape the recognition from CART-19 therapy...
June 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28394813/transforming-growth-factor-%C3%AE-is-a-poor-prognostic-factor-and-inhibits-the-favorable-prognostic-value-of-cd8-ctl-in-human-hepatocellular-carcinoma
#15
Chun-Yu Huang, Hua Wang, Wei Liao, Feng Han, Yong-Qiang Li, Shu-Wei Chen, Xiang-Ming Lao
It is widely understood that transforming growth factor β (TGF-β) has dual functions in tumors-tumor promoter or tumor suppressor. As a tumor promoter, TGF-β drives tumor initiation and progression partially by suppressing the antitumor responses of CD8 cytotoxic T lymphocytes (CTLs) in the tumor microenvironment. Here, we investigated the prognostic value of measuring TGF-β and CD8 CTLs levels and their relationship in human hepatocellular carcinoma (HCC). Immunohistochemical staining was conducted to analyze the prognostic value of TGF-β expression and/or CD8 CTLs levels in 407 HCC patients...
June 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28368960/ubiquitinated-proteins-isolated-from-tumor-cells-are-efficient-substrates-for-antigen-cross-presentation
#16
Guangjie Yu, Tarsem Moudgil, Zhihua Cui, Yongbin Mou, Lixin Wang, Bernard A Fox, Hong-Ming Hu
We have previously shown that inhibition of the proteasome causes defective ribosomal products to be shunted into autophagosomes and subsequently released from tumor cells as defective ribosomal products in Blebs (DRibbles). These DRibbles serve as an excellent source of antigens for cross-priming of tumor-specific T cells. Here, we examine the role of ubiquitinated proteins (Ub-proteins) in this pathway. Using purified Ub-proteins from tumor cells that express endogenous tumor-associated antigen or exogenous viral antigen, we tested the ability of these proteins to stimulate antigen-specific T-cell responses, by activation of monocyte-derived dendritic cells generated from human peripheral blood mononuclear cells...
June 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28338507/ny-eso-1-protein-cancer-vaccine-with-poly-iclc-and-ok-432-rapid-and-strong-induction-of-ny-eso-1-specific-immune-responses-by-poly-iclc
#17
Tomohira Takeoka, Hirotsugu Nagase, Koji Kurose, Yoshihiro Ohue, Makoto Yamasaki, Shuji Takiguchi, Eiichi Sato, Midori Isobe, Takayuki Kanazawa, Mitsunobu Matsumoto, Kota Iwahori, Atsunari Kawashima, Akiko Morimoto-Okazawa, Hiroyoshi Nishikawa, Mikio Oka, Linda Pan, Ralph Venhaus, Eiichi Nakayama, Masaki Mori, Yuichiro Doki, Hisashi Wada
We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28338506/a-preliminary-report-radical-surgery-and-stem-cell-transplantation-for-the-treatment-of-patients-with-pancreatic-cancer
#18
Brigitta Omazic, Burcu Ayoglu, Matthias Löhr, Ralf Segersvärd, Caroline Verbeke, Isabelle Magalhaes, Zuzana Potacova, Jonas Mattsson, Alexei Terman, Sam Ghazi, Nils Albiin, Nikolaos Kartalis, Peter Nilsson, Thomas Poiret, Liu Zhenjiang, Rainer Heuchel, Jochen M Schwenk, Johan Permert, Markus J Maeurer, Olle Ringden
We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT...
March 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28267050/nivolumab-causing-a-polymyalgia-rheumatica-in-a-patient-with-a-squamous-non-small-cell-lung-cancer
#19
Marjorie Bernier, Cyril Guillaume, Nathalie Leon, Joachim Alexandre, Lea Hamel-Senecal, Basile Chretien, Florian Lecaignec, Xavier Humbert, Sophie Fedrizzi, Jeannick Madelaine, Marion Sassier
The anti-programmed cell-death-1 antibody, nivolumab, has been recently approved for the treatment of advanced non-small cell lung cancer. Although, today, immune-related adverse effects such as dermatologic, digestive, hepatic, and endocrine toxicities are well-known with immune checkpoint inhibitors, rheumatic diseases are less well described. Herein, we report the case of a patient without a history of arthritis who developed polymyalgia rheumatica after 13 cycles of nivolumab used for the treatment of advanced non-small cell lung cancer...
March 6, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28234667/myasthenia-gravis-after-nivolumab-therapy-for-squamous-cell-carcinoma-of-the-bladder
#20
Elaine Chang, Anita L Sabichi, Yvonne H Sada
Checkpoint inhibitors have become standard therapy for multiple cancers, and their use will increase in the next year as regulatory approvals for additional indications are expected. It is essential for clinicians to be aware of the potential for rare immune-related adverse effects. Here, we report the case of a new diagnosis of myasthenia gravis (MG) after the use of nivolumab for squamous cell carcinoma of the bladder. A review the literature identified 10 cases of MG diagnosed after programmed cell death protein 1 inhibitor therapy...
February 23, 2017: Journal of Immunotherapy
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