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Journal of Immunotherapy

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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
#1
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...
April 7, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28368960/ubiquitinated-proteins-isolated-from-tumor-cells-are-efficient-substrates-for-antigen-cross-presentation
#2
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...
March 31, 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
#3
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
#4
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
#5
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
#6
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
https://www.readbyqxmd.com/read/28234666/a-novel-fusion-antibody-exhibits-antiangiogenic-activity-and-stimulates-nk-cell-mediated-immune-surveillance-through-fused-nkg2d-ligand
#7
Desmond O Acheampong, Mingying Tang, Youfu Wang, Xin Zhao, Wei Xie, Zhiguo Chen, Wenzhi Tian, Min Wang, Juan Zhang
A single-chain variable fragment (scFv) targeting vascular endothelial growth factor receptor 2 was previously generated from a phage display library in our laboratory. However, it has shortened half-life and lacks Fc fragment for effector cell recognition. To address these challenges, a ligand of NK-cell receptor NKG2D was fused to the scFv and created a fusion protein scFv-major histocompatibility complex class I-related chain A (MICA), which is expected to recognize tumor cells through the scFv moiety and stimulate NK cells through the MICA...
February 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28234665/possible-compartmental-cytokine-release-syndrome-in-a-patient-with-recurrent-ovarian-cancer-after-treatment-with-mesothelin-targeted-car-t-cells
#8
Janos L Tanyi, Caitlin Stashwick, Gabriela Plesa, Mark A Morgan, David Porter, Marcela V Maus, Carl H June
Cytokine release syndrome (CRS) is a potentially severe systemic toxicity seen after adoptive T-cell therapy and caused by T-cell activation and proliferation and is associated with elevated circulating levels of cytokines such as C-reactive protein, interleukin-6 (IL-6), and interferon-γ and has previously been described as a systemic response in hematologic malignancies. A 52-year-old woman with BRCA 1 mutation positive heavily pretreated advanced recurrent serous ovarian cancer was treated under a compassionate use protocol with autologous mesothelin-redirected chimeric antigen receptor T cells (CART-meso)...
February 23, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28221189/a-retrospective-analysis-of-the-efficacy-of-pembrolizumab-in-melanoma-patients-with-brain-metastasis
#9
Ibiayi Dagogo-Jack, Michael Lanfranchi, Justin F Gainor, Anita Giobbie-Hurder, Donald P Lawrence, Alice T Shaw, Ryan J Sullivan
A total of 50% of patients with melanoma will develop brain metastasis (BM). Pembrolizumab was approved for treatment of metastatic melanoma on the basis of significant systemic antitumor activity. Because of low enrollment of patients with BM in pembrolizumab trials, efficacy against melanoma BM remains unknown. We reviewed records of 89 consecutive patients with melanoma treated with pembrolizumab at our institution between May 1, 2014 and October 31, 2015 to determine the time to progression. Thirty-six (40%) patients had BM before pembrolizumab...
February 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28221188/treatment-of-cervical-intraepithelial-neoplasia-patients-preferences-for-surgery-or-immunotherapy-with-imiquimod
#10
Margot M Koeneman, Brigitte A Essers, Cornelis G Gerestein, Anna J M van de Sande, Rogier J N T M Litjens, Dieuwke Boskamp, Medi F J Goossens, Heleen J Beekhuizen, Roy F P M Kruitwagen, Arnold J Kruse, Carmen D Dirksen
OBJECTIVE: Imiquimod has been studied as a noninvasive pharmacological treatment alternative to large loop excision of the transformation zone (LLETZ) for high-grade cervical intraepithelial neoplasia (CIN), to prevent long-term obstetric complications from surgical treatment. This study aims to investigate womens' preferences for treatment of high-grade CIN with imiquimod or LLETZ. METHODS: A labeled discrete choice experiment was conducted among 100 women with abnormal cervical cytology in 5 hospitals in the Netherlands between March 2014 and December 2015...
February 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28166182/vogt-koyanagi-harada-like-syndrome-complicating-pembrolizumab-treatment-for-metastatic-melanoma
#11
Marion Bricout, Adeline Petre, Mona Amini-Adle, Widad Bezza, Pascal Seve, Laurent Kodjikian, Stéphane Dalle, Luc Thomas
Vogt-Koyanagi-Harada (VKH) syndrome is a rare condition implicating systemic immune reaction against melanocytes. The pathophysiology is unclear. A genetic predisposition has been suggested as HLA-DR4/DRB1*04 is more common among VKH patients. Drug induced VKH syndrome has been reported in advanced melanoma patients receiving immunotherapy, including ipilimumab and adoptive cell transfer of Tumor-Infiltrating Lymphocyte associated with IL-2. To date, no case of anti PD-1 -induced VKH syndrome has been described...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28166181/dna-vaccine-encoding-hpv16-oncogenes-e6-and-e7-induces-potent-cell-mediated-and-humoral-immunity-which-protects-in-tumor-challenge-and-drives-e7-expressing-skin-graft-rejection
#12
Janin Chandra, Julie L Dutton, Bo Li, Wai-Ping Woo, Yan Xu, Lynn K Tolley, Michelle Yong, James W Wells, Graham R Leggatt, Neil Finlayson, Ian H Frazer
We have previously shown that a novel DNA vaccine technology of codon optimization and the addition of ubiquitin sequences enhanced immunogenicity of a herpes simplex virus 2 polynucleotide vaccine in mice, and induced cell-mediated immunity when administered in humans at relatively low doses of naked DNA. We here show that a new polynucleotide vaccine using the same technology and encoding a fusion protein of the E6 and E7 oncogenes of high-risk human papillomavirus type 16 (HPV16) is immunogenic in mice. This vaccine induces long-lasting humoral and cell-mediated immunity and protects mice from establishment of HPV16-E7-expressing tumors...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28166180/therapeutic-vaccine-against-primate-papillomavirus-infections-of-the-cervix
#13
Emeline Ragonnaud, Anne-Marie C Andersson, Silmi Mariya, Anders G Pedersen, Robert D Burk, Antonella Folgori, Stefano Colloca, Riccardo Cortese, Alfredo Nicosia, Joko Pamungkas, Diah Iskandriati, Peter J Holst
Currently available prophylactic vaccines have no therapeutic efficacy for preexisting human papillomavirus (HPVs) infections, do not target all oncogenic HPVs and are insufficient to eliminate the burden of HPV induced cancer. We aim to develop an alternative HPV vaccine which is broadly effective and capable of clearing preexisting infection. In an initial attempt to develop a broadly reactive therapeutic vaccine, we designed a putative papillomavirus (PV) ancestor antigen (circulating sequence derived antigenic sequences E1E2-CDSE1E2) based on the conserved E1 and E2 protein sequences from existing oncogenic HPV strains...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28125513/a-dendritic-cell-vaccine-combined-with-radiotherapy-activates-the-specific-immune-response-in-patients-with-esophageal-cancer
#14
Chengshi Wang, Juan Pu, Hanxu Yu, Yanyan Liu, Honghuan Yan, Zhongxiang He, Xin Feng
Dendritic cells (DC) are highly efficient antigen-presenting cells. DC may be used to create DC vaccines against cancer, but the optimal strategies remain to be elucidated. This study aimed to examine the benefits and adverse effects of using esophageal cancer cell antigens to stimulate DC to trigger the specific immune response in patients with esophageal cancer undergoing radiotherapy. This was an observational cohort study performed at Lianshui County People's Hospital between September 2010 and June 2012...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28005579/spontaneous-activation-of-antigen-presenting-cells-by-genes-encoding-truncated-homo-oligomerizing-derivatives-of-cd40
#15
Noam Levin, Aviad Pato, Gal Cafri, Galit Eisenberg, Tamar Peretz, Alon Margalit, Michal Lotem, Gideon Gross
The interaction between the CD40 receptor on antigen-presenting cells (APCs) and its trimeric ligand on CD4 T cells is essential for the initiation and progression of the adaptive immune response. Here we undertook to endow CD40 with the capacity to trigger spontaneous APC activation through ligand-independent oligomerization. To this end we exploited the GCN4 yeast transcriptional activator, which contains a leucine zipper DNA-binding motif that induces homophilic interactions. We incorporated GCN4 variants forming homodimers, trimers, or tetramers at the intracellular domain of human and mouse CD40 and replaced the extracellular portion with peptide-β2m or other peptide tags...
February 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28125512/superior-suppression-of-erbb2-positive-tumor-cells-by-a-novel-human-triparatopic-tribody
#16
Gennaro Riccio, Ana R Da Fonseca-Ricardo, Margherita Passariello, Philip Cunnah, Nico Mertens, Claudia De Lorenzo
Downregulation of the epidermal growth factor receptor family of receptors is improved by combining different antibodies to noncompetitive epitopes. For ErbB2/HER2 this has already been translated into clinical practice by using a combination of trastuzumab and pertuzumab. Moreover, cocktails of 2 or 3 anti-epidermal growth factor receptor antibodies show an enhanced downregulation of the receptor due to the induction of matrix formation. A more efficient method for inducing matrix formation and receptor downregulation might include the use of trispecific reagents...
January 25, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28099196/use-of-engineered-exosomes-expressing-hla-and-costimulatory-molecules-to-generate-antigen-specific-cd8-t-cells-for-adoptive-cell-therapy
#17
Sueon Kim, Hyun-Jung Sohn, Hyun-Joo Lee, Dae-Hee Sohn, Seung-Joo Hyun, Hyun-Il Cho, Tai-Gyu Kim
Dendritic cell-derived exosomes (DEX) comprise an efficient stimulator of T cells. However, the production of sufficient DEX remains a barrier to their broad applicability in immunotherapeutic approaches. In previous studies, genetically engineered K562 have been used to generate artificial antigen presenting cells (AAPC). Here, we isolated exosomes from K562 cells (referred to as CoEX-A2s) engineered to express human leukocyte antigen (HLA)-A2 and costimulatory molecules such as CD80, CD83, and 41BBL. CoEX-A2s were capable of stimulating antigen-specific CD8 T cells both directly and indirectly via CoEX-A2 cross-dressed cells...
January 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27875387/clinical-response-rates-from-interleukin-2-therapy-for-metastatic-melanoma-over-30-years-experience-a-meta-analysis-of-3312-patients
#18
Richard Bright, Brendon J Coventry, Nathan Eardley-Harris, Nancy Briggs
Interleukin-2 (IL-2), initially used in 1986, can induce clinical regression-complete responses (CR) and partial responses (PR) of metastatic malignant melanoma. IL-2 has been used alone or in combination, and in different dosage schedules, as an immunotherapeutic agent for melanoma treatment. This meta-analysis aimed to document and evaluate the spectrum of reported clinical response rates from the combined experience of almost 30 years of IL-2 clinical usage. Clinical trials using IL-2 for metastatic melanoma therapy that reported: dosage, combinations, study details, definitions and clinical CR, PR, and overall response (OR) rates were included...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27846054/sequencing-treatment-in-brafv600-mutant-melanoma-anti-pd-1-before-and-after-braf-inhibition
#19
Douglas B Johnson, Eirini Pectasides, Emily Feld, Fei Ye, Shilin Zhao, Romany Johnpulle, Ryan Merritt, David F McDermott, Igor Puzanov, Donald Lawrence, Jeffrey A Sosman, Elizabeth Buchbinder, Ryan J Sullivan
Novel agents targeting immune checkpoint molecules or mutated BRAF are active therapeutic options for patients with BRAF-mutant melanoma. However, the most effective first-line treatment and the optimal sequencing of these agents have not been well characterized. To explore this, we retrospectively assessed 114 patients from 4 centers with advanced, BRAF-mutant melanoma who received anti-programmed cell death-1 (PD-1)/PD-L1 antibodies. We evaluated clinical outcomes, including objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) to initial and subsequent therapies in patients that received anti-PD-1 first (n=56) versus those that received BRAF±MEK inhibitors (BRAFi) first (n=58)...
January 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27828929/the-characteristics-of-naive-like-t-cells-in-tumor-infiltrating-lymphocytes-from-human-lung-cancer
#20
Si Yuan Sheng, Yong Gu, Chuan Gang Lu, Ying Ying Tang, Jian Yong Zou, Yu Qing Zhang, Rong Fu Wang, Hai Hong
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TILs) or genetically modified lymphocytes from TILs is a new effective approach, but the application of TIL immunotherapy is still limited in many solid tumors. Knowledge of the classification and function of TILs is important to develop personalized immunotherapy with TILs in non-small lung cancer (NSCLC). In this study, we show the characteristics of T-cell subsets in TILs isolated from NSCLC. CD3 CD8 CD45RA T cells outnumbered CD3 CD4 CD45RA T cells in CD45RA TILs, but it was the opposite in CD45RO TILs...
January 2017: Journal of Immunotherapy
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