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Journal of Immunotherapy

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https://www.readbyqxmd.com/read/29781826/understanding-microbiome-effect-on-immune-checkpoint-inhibition-in-lung-cancer-placing-the-puzzle-pieces-together
#1
Umang Swami, Yousef Zakharia, Jun Zhang
Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations...
May 17, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29757889/utilizing-t-cell-activation-signals-1-2-and-3-for-tumor-infiltrating-lymphocytes-til-expansion-the-advantage-over-the-sole-use-of-interleukin-2-in-cutaneous-and-uveal-melanoma
#2
René J Tavera, Marie-Andrée Forget, Young Uk Kim, Donastas Sakellariou-Thompson, Caitlin A Creasy, Ankit Bhatta, Orenthial J Fulbright, Renjith Ramachandran, Shawne T Thorsen, Esteban Flores, Arely Wahl, Audrey M Gonzalez, Christopher Toth, Seth Wardell, Rahmatu Mansaray, Laszlo G Radvanyi, Dan S Gombos, Sapna P Patel, Patrick Hwu, Rodabe N Amaria, Chantale Bernatchez, Cara Haymaker
In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8 TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8CD3 TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in <3 weeks...
May 11, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29742520/ipilimumab-nivolumab-related-opsoclonus-myoclonus-ataxia-syndrome-variant-in-a-patient-with-malignant-pleural-mesothelioma
#3
Bradley Maller, Edwin Peguero, Tawee Tanvetyanon
INTRODUCTION: Ipilimumab and nivolumab are immune-checkpoint inhibitors commonly used for melanoma. The combination is being investigated for its efficacy against several types of cancer, including malignant pleural mesothelioma. Although immune-related adverse events have been reported in patients receiving immune-checkpoint inhibitors, opsoclonus-myoclonus-ataxia syndrome has never been previously described. CASE PRESENTATION: We describe a 74-year-old male with malignant pleural mesothelioma who presented with opsoclonus and marked truncal ataxia ∼10 weeks following immunotherapy with ipilimumab and nivolumab...
May 8, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29683892/implication-of-highly-cytotoxic-natural-killer-cells-for-esophageal-squamous-cell-carcinoma-treatment
#4
Kee Siang Lim, Kosaku Mimura, Ley-Fang Kua, Kensuke Shiraishi, Koji Kono
Esophageal squamous cell carcinoma (ESCC) is an aggressive upper gastrointestinal cancer and effective treatments are limited. Previous studies reported that natural killer (NK) cells expanded by coculturing with K562-mb15-41BBL feeder cells, a genetically modified K562 leukemia cell line that expresses membrane-bound interleukin (IL)-15 and 41BBL ligand, were highly proliferative and highly cytotoxic. Here, we investigated the potential of expanded NK cells for ESCC treatment. We analyzed both genetic and surface expression levels of NKG2D ligands (NKG2DLs) in ESCC using publicly available microarray data sets and ESCC cell lines...
April 20, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29683891/il-21-increases-the-reactivity-of-allogeneic-human-v%C3%AE-9v%C3%AE-2-t-cells-against-primary-glioblastoma-tumors
#5
Noémie Joalland, Cynthia Chauvin, Lisa Oliver, François M Vallette, Claire Pecqueur, Ulrich Jarry, Emmanuel Scotet
Glioblastoma multiforme (GBM) remains the most frequent and deadliest primary brain tumor in adults despite aggressive treatments, because of the persistence of infiltrative and resistant tumor cells. Nonalloreactive human Vγ9Vδ2 T lymphocytes, the major peripheral γδ T-cell subset in adults, represent attractive effectors for designing immunotherapeutic strategies to track and eliminate brain tumor cells, with limited side effects. We analyzed the effects of ex vivo sensitizations of Vγ9Vδ2 T cells by IL-21, a modulating cytokine, on their cytolytic reactivity...
April 20, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29683890/characteristics-and-predictive-value-of-pd-l1-status-in-real-world-non-small-cell-lung-cancer-patients
#6
Jeng-Sen Tseng, Tsung-Ying Yang, Chih-Ying Wu, Wen-Hui Ku, Kun-Chieh Chen, Kuo-Hsuan Hsu, Yen-Hsiang Huang, Kang-Yi Su, Sung-Liang Yu, Gee-Chen Chang
Immunotherapy targeting the programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway has emerged as an effective treatment for lung cancer patients. It is important to evaluate the practicality of PD-L1 testing in real-world practice. A total of 211 non-small cell lung cancer patients were enrolled to detect 5 driver mutations and PD-L1 status (22C3 and SP263 assays) and to evaluate the characteristics of PD-L1 expression and its predictive value of immunotherapy. The PD-L1 positive (≥1%) and strong positive (≥50%) rate by SP263 assay was 27...
April 20, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29672342/outcomes-of-adoptive-cell-transfer-with-tumor-infiltrating-lymphocytes-for-metastatic-melanoma-patients-with-and-without-brain-metastases
#7
Gautam U Mehta, Parisa Malekzadeh, Thomas Shelton, Donald E White, John A Butman, James C Yang, Udai S Kammula, Stephanie L Goff, Steven A Rosenberg, Richard M Sherry
Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous melanoma, the efficacy of this therapy for brain metastases is unclear. Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain metastases, were analyzed. Treatment consisted of preparative chemotherapy, autologous TIL infusion, and high-dose interleukin-2...
April 18, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29668571/evaluating-for-pseudoprogression-in-colorectal-and-pancreatic-tumors-treated-with-immunotherapy
#8
Christine M Parseghian, Madhavi Patnana, Priya Bhosale, Kenneth R Hess, Ya-Chen Tina Shih, Bumyang Kim, Scott Kopetz, Michael J Overman, Gauri R Varadhachary, Milind Javle, Aung Naing, Sarina Piha-Paul, David Hong, Hung Le, Vivek Subbiah, Shubham Pant
Pseudoprogression has been observed in patients with various tumor types treated with immunotherapy. However, the frequency of pseudoprogression is unknown in gastrointestinal malignancies. Metastatic colorectal cancer (mCRC) and advanced pancreatic ductal adenocarcinoma (PDAC) patients who progressed on treatment with immunotherapy beyond RECIST version 1.1 criteria were analyzed. Degree of progression, tumor markers, time to progression, overall survival, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and costs were analyzed for patients treated beyond progression (TBP) and not treated beyond progression...
April 17, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29642086/evidence-for-efficacy-of-treatment-with-the-anti-pd-1-mab-nivolumab-in-radiation-and-multichemorefractory-advanced-penile-squamous-cell-carcinoma
#9
Dimitrios T Trafalis, Constantinos E Alifieris, Anastasios Kalantzis, Kosmas E Verigos, Chrysovalantis Vergadis, Sébastien Sauvage
Penile squamous cell carcinoma (PeSCC) is a rare tumor and advanced PeSCC is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. We describe for the first time a case with advanced chemoradiation refractory PeSCC who had documented response to active immunotherapy with the immune checkpoint inhibitor, anti-programmed death-1 monoclonal antibody Nivolumab. The patient suffered from a poor prognosis human papillomavirus-negative PeSCC, with a somatic inactivation mutation of cyclin-dependent kinase inhibitor 2A (CDKN2A) gene in tumor cells, and treatment with Nivolumab resulted in a partial response to therapy and significant tumor shrinkage...
April 10, 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29481423/diabetes-and-blood-glucose-disorders-under-anti-pd1
#10
Quentin Magis, Caroline Gaudy-Marqueste, Agnes Basire, Anderson Loundou, Nausicaa Malissen, Laura Troin, Sandrine Monestier, Stéphanie Mallet, Sylvie Hesse, Marie-Aleth Richard, René Valéro, Sophie Beliard, Jean-Jacques Grob
Acute type 1 diabetes (AD1) is a rare but definitive immune-related adverse event associated with anti-PD1. Most of the reported cases are close to what has been described as "fulminant type 1 diabetes." We sought to determine whether anti-PD1 could impair glycoregulation and whether occurrence of AD1 could be anticipated by prior glycemic changes. Fasting glycemia collected before, under, and after treatment in melanoma patients treated with anti-PD1 over a period of 36 months were retrospectively analyzed...
June 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29470191/characterization-of-postinfusion-phenotypic-differences-in-fresh-versus-cryopreserved-tcr-engineered-adoptive-cell-therapy-products
#11
Theodore S Nowicki, Helena Escuin-Ordinas, Earl Avramis, Bartosz Chmielowski, Thinle Chodon, Beata Berent-Maoz, Xiaoyan Wang, Paula Kaplan-Lefko, Lili Yang, David Baltimore, James S Economou, Antoni Ribas, Begoña Comin-Anduix
Adoptive cell therapy (ACT) consisting of genetically engineered T cells expressing tumor antigen-specific T-cell receptors displays robust initial antitumor activity, followed by loss of T-cell activity/persistence and frequent disease relapse. We characterized baseline and longitudinal T-cell phenotype variations resulting from different manufacturing and administration protocols in patients who received ACT. Patients with melanoma who enrolled in the F5-MART-1 clinical trial (NCT00910650) received infusions of MART-1 T-cell receptors transgenic T cells with MART-1 peptide-pulsed dendritic cell vaccination...
June 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29432282/phase-i-study-of-multiple-epitope-peptide-vaccination-in-patients-with-recurrent-or-persistent-cervical-cancer
#12
Kosei Hasegawa, Yuji Ikeda, Yuko Kunugi, Akira Kurosaki, Yuichi Imai, Shunsuke Kohyama, Shoji Nagao, Eito Kozawa, Koji Yoshida, Takuya Tsunoda, Yusuke Nakamura, Keiichi Fujiwara
Cancer immunotherapy has now been established as a leading standard therapeutic option in a subset of patients with cancer. In this study, we conducted a phase I dose-escalation trial using a mixture of 5 peptides to vaccinate cervical cancer patients with HLA-A*2402. The primary endpoints were safety and determination of a recommended vaccine dose, and the secondary endpoints were evaluations of immunologic responses and clinical efficacy. All patients had recurrent or persistent disease and had failed to respond to or were intolerant to prior standard chemotherapy...
May 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29334492/anti-il-10-mediated-enhancement-of-antitumor-efficacy-of-a-dendritic-cell-targeting-mip3%C3%AE-gp100-vaccine-in-the-b16f10-mouse-melanoma-model-is-dependent-on-type-i-interferons
#13
James T Gordy, Kun Luo, Brian Francica, Charles Drake, Richard B Markham
The chemokine MIP3α (CCL20) binds to CCR6 on immature dendritic cells. Vaccines fusing MIP3α to gp100 have been shown to be effective in therapeutically reducing melanoma tumor burden and prolonging survival in a mouse model. Other studies have provided evidence that interleukin-10 (IL-10) neutralizing antibodies (αIL-10) enhance immunologic melanoma therapies by modulating the tolerogenic tumor microenvironment. In the current study, we have utilized the B16F10 syngeneic mouse melanoma model to demonstrate for the first time that a therapy neutralizing IL-10 enhances the antitumor efficacy of a MIP3α-gp100 DNA vaccine, leading to significantly smaller tumors, slower growing tumors, and overall increases in mouse survival...
May 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29528991/whole-recombinant-saccharomyces-cerevisiae-yeast-expressing-ras-mutations-as-treatment-for-patients-with-solid-tumors-bearing-ras-mutations-results-from-a-phase-1-trial
#14
Allen Cohn, Michael A Morse, Bert O'Neil, Samuel Whiting, Claire Coeshott, John Ferraro, Donald Bellgrau, David Apelian, Timothy C Rodell
We are developing whole, heat-killed, recombinant Saccharomyces cerevisiae yeast, engineered to encode target proteins, which stimulate immune responses against malignant cells expressing those targets. This phase 1 trial, enrolling patients with advanced colorectal or pancreas cancer, was designed to evaluate safety, immunogenicity, response, and overall survival of ascending doses of the GI-4000 series of products, which express 3 different forms of mutated Ras proteins. The study enrolled 33 heavily pretreated subjects (14 with pancreas and 19 with colorectal cancer), whose tumors were genotyped before enrollment to identify the specific ras mutation and thereby to identify which GI-4000 product to administer...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29528990/nkg2d-immunoligand-rg7s-mica-enhances-nk-cell-mediated-immunosurveillance-in-colorectal-carcinoma
#15
Tong Wang, Fumou Sun, Yang Wang, Jiahao Jiang, Mingzhu Pan, Minne Yuan, Hang Zhang, Xiaodian Du, Kamal Hezam, Kai Song, Min Wang, Juan Zhang
Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29517616/a-dose-escalation-study-of-recombinant-human-interleukin-18-in-combination-with-ofatumumab-after-autologous-peripheral-blood-stem-cell-transplantation-for-lymphoma
#16
Michael J Robertson, Christopher W Stamatkin, David Pelloso, Jill Weisenbach, Nagendra K Prasad, Ahmad R Safa
Interleukin-18 (IL-18) is an immunostimulatory cytokine that augments antibody-dependent cellular cytotoxicity mediated by human natural killer cells against antibody-coated lymphoma cells in vitro and that has antitumor activity in animal models. Ofatumumab is a CD20 monoclonal antibody with activity against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20 lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29401166/the-risk-of-diarrhea-and-colitis-in-patients-with-advanced-melanoma-undergoing-immune-checkpoint-inhibitor-therapy-a-systematic-review-and-meta-analysis
#17
Parul Tandon, Samuel Bourassa-Blanchette, Kirles Bishay, Simon Parlow, Scott A Laurie, Jeffrey D McCurdy
Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti-programmed death-1 (PD-1) or anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29401165/hmgn2-an-antitumor-effector-molecule-of-%C3%AE-%C3%AE-t-cells
#18
Jiao Chen, Yaping Fan, Bomiao Cui, Xiaoying Li, Yu Yu, Yue Du, Qianming Chen, Yun Feng, Ping Zhang
γδT cells function in the regulation of T-cell activation in cancer and have been identified as a novel target for cancer immunotherapy. Activated γδT cells release a series of cytotoxic molecules-including granulysin, perforin, Fas/Fas ligand (Fas-L), and granzymes A and B-to kill target cells. Our previous research has shown that high mobility group nucleosomal-binding domain 2 (HMGN2), which is expressed at a high level in activated CD8T cells, is an antitumor effector molecule of CD8T cells. In the present study, we examined the expression and antitumor effects of HMGN2 in γδT cells...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29309291/bullous-pemphigoid-like-skin-lesions-and-overt-eosinophilia-in-a-patient-with-melanoma-treated-with-nivolumab-case-report-and-review-of-the-literature
#19
Amalia Anastasopoulou, Georgios Papaxoinis, Panagiotis Diamantopoulos, Erietta Christofidou, Olga Benopoulou, Alexandros Stratigos, Helen Gogas
The widespread use of immune checkpoint inhibitors has shed light to several unusual immune-related adverse effects of the drugs. Severe cutaneous adverse reactions are generally rare with anti-PD1 agents. We present in this paper the case of a 48-year-old patient with melanoma who developed bullous pemphigoid-like skin lesions along with fever, arthralgia and overt eosinophilia following adjuvant treatment with nivolumab. The condition was successfully treated with corticosteroids and a rechallenge with another anti-PD1 agent did not lead to recurrence of the skin lesions...
April 2018: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29293165/brief-communication-a-heterologous-oncolytic-bacteria-virus-prime-boost-approach-for-anticancer-vaccination-in-mice
#20
Amelia S Aitken, Dominic G Roy, Nikolas T Martin, Subash Sad, John C Bell, Marie-Claude Bourgeois-Daigneault
Anticancer vaccination is becoming a popular therapeutic approach for patients with cancers expressing common tumor antigens. One variation on this strategy is a heterologous virus vaccine where 2 viruses encoding the same tumor antigen are administered sequentially to prime and boost antitumor immunity. This approach is currently undergoing clinical investigation using an adenovirus (Ad) and the oncolytic virus Maraba (MRB). In this study, we show that Listeria monocytogenes can be used in place of the Ad to obtain comparable immune priming efficiency before MRB boosting...
April 2018: Journal of Immunotherapy
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