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JOURNAL ARTICLE
Hubert Lam, Lisa K McNeil, Hanna Starobinets, Victoria L DeVault, Roger B Cohen, Przemyslaw Twardowski, Melissa L Johnson, Maura L Gillison, Mark N Stein, Ulka N Vaishampayan, Arthur P DeCillis, James J Foti, Vijetha Vemulapalli, Emily Tjon, Kyle Ferber, Daniel B DeOliveira, Wendy Broom, Parul Agnihotri, Elizabeth M Jaffee, Kwok-Kin Wong, Charles G Drake, Pamela M Carroll, Thomas A Davis, Jessica Baker Flechtner
Neoantigens are critical targets of antitumor T-cell responses. The ATLAS bioassay was developed to identify neoantigens empirically by expressing each unique patient-specific tumor mutation individually in Escherichia coli , pulsing autologous dendritic cells in an ordered array, and testing the patient's T cells for recognition in an overnight assay. Profiling of T cells from patients with lung cancer revealed both stimulatory and inhibitory responses to individual neoantigens. In the murine B16F10 melanoma model, therapeutic immunization with ATLAS-identified stimulatory neoantigens protected animals, whereas immunization with peptides associated with inhibitory ATLAS responses resulted in accelerated tumor growth and abolished efficacy of an otherwise protective vaccine...
March 2021: Cancer Discovery
#22
REVIEW
Andres M Salazar, Esteban Celis
Relatively simple, synthetic, double-stranded RNAs can be powerful viral pathogen-associated molecular pattern (PAMP) mimics, inducing a panoply of antiviral and antitumor responses that act at multiple stages of host defense. Their mechanisms of action and uses are beginning to be understood, alone, in combination with other therapeutics, or as novel PAMP-adjuvants providing the critical danger signal that has been missing from most cancer and other modern vaccines. Dose, timing, route of administration combinations, and other clinical variables can have a critical impact on immunogenicity...
November 2020: Urologic Clinics of North America
#23
JOURNAL ARTICLE
Nicholas F Page, Michael J Gandal, Myka L Estes, Scott Cameron, Jessie Buth, Sepideh Parhami, Gokul Ramaswami, Karl Murray, David G Amaral, Judy A Van de Water, Cynthia M Schumann, Cameron S Carter, Melissa D Bauman, A Kimberley McAllister, Daniel H Geschwind
BACKGROUND: Maternal immune activation (MIA) is a proposed risk factor for multiple neuropsychiatric disorders, including schizophrenia. However, the molecular mechanisms through which MIA imparts risk remain poorly understood. A recently developed nonhuman primate model of exposure to the viral mimic poly:ICLC during pregnancy shows abnormal social and repetitive behaviors and elevated striatal dopamine, a molecular hallmark of human psychosis, providing an unprecedented opportunity for studying underlying molecular correlates...
May 1, 2021: Biological Psychiatry
#24
REVIEW
Hussein Sultan, Andres M Salazar, Esteban Celis
Immunotherapies have become the first line of treatment for many cancer types. Unfortunately, only a small fraction of patients benefits from these therapies. This low rate of success can be attributed to 3 main barriers: 1) low frequency of anti-tumor specific T cells; 2) lack of infiltration of the anti-tumor specific T cells into the tumor parenchyma and 3) accumulation of highly suppressive cells in the tumor mass that inhibit the effector function of the anti-tumor specific T cells. Thus, the identification of immunomodulators that can increase the frequency and/or the infiltration of antitumor specific T cells while reducing the suppressive capacity of the tumor microenvironment is necessary to ensure the effectiveness of T cell immunotherapies...
September 30, 2020: Seminars in Immunology
#25
JOURNAL ARTICLE
Sabine Mueller, Jared M Taitt, Javier E Villanueva-Meyer, Erin R Bonner, Takahide Nejo, Rishi R Lulla, Stewart Goldman, Anu Banerjee, Susan N Chi, Nicholas S Whipple, John R Crawford, Karen Gauvain, Kellie J Nazemi, Payal B Watchmaker, Neil D Almeida, Kaori Okada, Andres M Salazar, Ryan D Gilbert, Javad Nazarian, Annette M Molinaro, Lisa H Butterfield, Michael D Prados, Hideho Okada
BACKGROUNDPatients with diffuse midline gliomas (DMGs), including diffuse intrinsic pontine glioma (DIPG), have dismal outcomes. We previously described the H3.3K27M mutation as a shared neoantigen in HLA-A*02.01+, H3.3K27M+ DMGs. Within the Pacific Pediatric Neuro-Oncology Consortium, we assessed the safety and efficacy of an H3.3K27M-targeted peptide vaccine.METHODSNewly diagnosed patients, aged 3-21 years, with HLA-A*02.01+ and H3.3K27M+ status were enrolled in stratum A (DIPG) or stratum B (nonpontine DMG)...
December 1, 2020: Journal of Clinical Investigation
#26
JOURNAL ARTICLE
Thi-Anh-Thuy Tran, Young-Hee Kim, Thi-Hoang-Oanh Duong, Shin Jung, In-Young Kim, Kyung-Sub Moon, Woo-Youl Jang, Hyun-Ju Lee, Je-Jung Lee, Tae-Young Jung
Glioblastoma, the most common aggressive cancer, has a poor prognosis. Among the current standard treatment strategies, radiation therapy is the most commonly recommended. However, it is often unsuccessful at completely eliminating the cancer from the brain. A combination of radiation with other treatment methods should therefore be considered. It has been reported that radiotherapy in combination with immunotherapy might show a synergistic effect; however, this still needs to be investigated. In the current study, a "branched multipeptide and peptide adjuvants [such as pan DR epitope (PADRE) and polyinosinic-polycytidylic acid-stabilized with polylysine and carboxymethylcellulose-(poly-ICLC)]," namely vaccine and anti-PD1, were used as components of immunotherapy to assist in the anti-tumor effects of radiotherapy against glioblastomas...
2020: Frontiers in Immunology
#27
JOURNAL ARTICLE
Laura Arribillaga, Iciar Echeverria, Viriginia Belsue, Timothy Gomez, Teresa Lozano, Noelia Casares, Lorea Villanueva, Sonia Domingos-Pereira, Pedro J Romero, Denise Nardelli-Haefliger, Sandra Hervás-Stubbs, Pablo Sarobe, María Josefa Rodriguez, José L Carrascosa, Thomas Zürcher, Juan José Lasarte
BACKGROUND: In vivo targeting of human papillomavirus (HPV) derived antigens to dendritic cells might constitute an efficient immunotherapeutic strategy against cervical cancer. In previous works, we have shown that the extra domain A from murine fibronectin (mEDA) can be used to target antigens to toll-like receptor 4 (TLR4) expressing dendritic cells and induce strong antigen-specific immune responses. In the present study, we have produced a bivalent therapeutic vaccine candidate consisting of the human EDA (hEDA) fused to E7 proteins from HPV16 and HPV18 (hEDA-HPVE7-16/18) and evaluate its potential as a therapeutic vaccine against cervical cancer...
June 2020: Journal for Immunotherapy of Cancer
#28
JOURNAL ARTICLE
Victor H Engelhard, Rebecca C Obeng, Kara L Cummings, Gina R Petroni, Angela L Ambakhutwala, Kimberly A Chianese-Bullock, Kelly T Smith, Amanda Lulu, Nikole Varhegyi, Mark E Smolkin, Paisley Myers, Keira E Mahoney, Jeffrey Shabanowitz, Nico Buettner, Emily H Hall, Kathleen Haden, Mark Cobbold, Donald F Hunt, Geoffrey Weiss, Elizabeth Gaughan, Craig L Slingluff
BACKGROUND: Phosphorylated peptides presented by MHC molecules represent a new class of neoantigens expressed on cancer cells and recognized by CD8 T-cells. These peptides are promising targets for cancer immunotherapy. Previous work identified an HLA-A*0201-restricted phosphopeptide from insulin receptor substrate 2 (pIRS2) as one such target. The purpose of this study was to characterize a second phosphopeptide, from breast cancer antiestrogen resistance 3 (BCAR3), and to evaluate safety and immunogenicity of a novel immunotherapic vaccine comprising either or both of these phosphorylated peptides...
May 2020: Journal for Immunotherapy of Cancer
#29
JOURNAL ARTICLE
Masao Nakajima, Shoichi Hazama, Koji Tamada, Keiko Udaka, Yasunobu Kouki, Toshinari Uematsu, Hideki Arima, Akira Saito, Shun Doi, Hiroto Matsui, Yoshitaro Shindo, Satoshi Matsukuma, Shinsuke Kanekiyo, Yukio Tokumitsu, Shinobu Tomochika, Michihisa Iida, Shin Yoshida, Yuki Nakagami, Nobuaki Suzuki, Shigeru Takeda, Shigeru Yamamoto, Shigefumi Yoshino, Tomio Ueno, Hiroaki Nagano
BACKGROUND: This phase I study aimed to evaluate the safety, peptide-specific immune responses, and anti-tumor effects of a novel vaccination therapy comprising multi-HLA-binding heat shock protein (HSP) 70/glypican-3 (GPC3) peptides and a novel adjuvant combination of hLAG-3Ig and Poly-ICLC against metastatic gastrointestinal cancers. METHODS: HSP70/GPC3 peptides with high binding affinities for three HLA types (A*24:02, A*02:01, and A*02:06) were identified with our peptide prediction system...
March 26, 2020: Cancer Immunology, Immunotherapy: CII
#30
JOURNAL ARTICLE
Anna Pavlick, Ana B Blazquez, Marcia Meseck, Michael Lattanzi, Patrick A Ott, Thomas U Marron, Rose Marie Holman, John Mandeli, Andres M Salazar, Christopher B McClain, Gustavo Gimenez, Sreekumar Balan, Sacha Gnjatic, Rachel Lubong Sabado, Nina Bhardwaj
Given its ability to induce both humoral and cellular immune responses, NY-ESO-1 has been considered a suitable antigen for a cancer vaccine. Despite promising results from early-phase clinical studies in melanoma patients, NY-ESO-1 vaccine immunotherapy has not been widely investigated in larger trials; consequently, many questions remain as to the optimal vaccine formulation, predictive biomarkers, and sequencing and timing of vaccines in melanoma treatment. We conducted an adjuvant phase I/II clinical trial in high-risk resected melanoma to optimize the delivery of poly-ICLC, a TLR-3/MDA-5 agonist as a component of vaccine formulation...
November 7, 2019: Cancer Immunology Research
#31
JOURNAL ARTICLE
Isabel Vivas, Kristina Iribarren, Teresa Lozano, David Cano, Aritz Lasarte-Cia, Silvia Chocarro, Marta Gorraiz, Pablo Sarobe, Sandra Hervás-Stubbs, Javier Ignacio Bilbao, Noelia Casares, Juan José Lasarte
PURPOSE: To evaluate the therapeutic efficacy of irreversible electroporation (IRE) combined with the intratumoral injection of the immunogenic adjuvant poly-ICLC (polyinosinic-polycytidylic acid and poly-L-lysine, a dsRNA analog mimicking viral RNA) inmediately before IRE. MATERIALS AND METHODS: Mice and rabbits bearing hepatocellular carcinoma tumors (Hepa.129 and VX2 tumor models, respectively) were treated with IRE (2 pulses of 2500V), with poly-ICLC, or with IRE + poly-ICLC combination therapy...
May 14, 2019: Journal of Vascular and Interventional Radiology: JVIR
#32
JOURNAL ARTICLE
Mansi Saxena, Rachel L Sabado, Melissa La Mar, Hiroshi Mohri, Andres M Salazar, Hanqing Dong, Joel Correa Da Rosa, Martin Markowitz, Nina Bhardwaj, Elizabeth Miller
Objective: Toll-like receptor-3 agonist Poly-ICLC has been known to activate immune cells and induce HIV replication in pre-clinical experiments. In this study we investigated if Poly-ICLC could be used for disrupting HIV latency while simultaneously enhancing innate immune responses. Design: This was a randomized, placebo-controlled, double-blinded trial in aviremic, cART-treated HIV-infected subjects. Participants ( n = 15) were randomized 3:1 to receive two consecutive daily doses of Poly-ICLC (1.4 mg subcutaneously) vs...
2019: Frontiers in Immunology
#33
JOURNAL ARTICLE
Emma Boydell, Eliana Marinari, Denis Migliorini, Pierre-Yves Dietrich, Anna Patrikidou, Valérie Dutoit
Immunotherapy, including therapeutic vaccines, is increasingly being developed for patients with high-grade glioma, and combinations of immunotherapies and synergy with standard of care are being investigated. In this regard, bevacizumab (BEV) has been shown to synergize with immunotherapy in preclinical studies of glioma and in other tumour entities. Here, we conducted a post-hoc exploratory study to evaluate the effect of the IMA950/poly-ICLC peptide vaccine on subsequent BEV administration in high-grade glioma patients...
April 2, 2019: Cancers
#34
JOURNAL ARTICLE
Denis Migliorini, Valérie Dutoit, Mathilde Allard, Nicole Grandjean Hallez, Eliana Marinari, Valérie Widmer, Géraldine Philippin, Francesca Corlazzoli, Robin Gustave, Mario Kreutzfeldt, Nathalie Blazek, Joëlle Wasem, Andreas Hottinger, Avinash Koka, Shahan Momjian, Alexander Lobrinus, Doron Merkler, Maria-Isabel Vargas, Paul R Walker, Anna Patrikidou, Pierre-Yves Dietrich
BACKGROUND: Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC (polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose) in human leukocyte antigen A2+ glioma patients. METHODS: Adult patients with newly diagnosed glioblastoma (n = 16) and grade III astrocytoma (n = 3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination...
July 11, 2019: Neuro-oncology
#35
JOURNAL ARTICLE
Meir Kende, Jason Paragas, Andres M Salazar
The potential protection of poly-ICLC (Hiltonol® ) a double stranded RNA (dsRNA) against EZV infection was assessed with prophylactic and therapeutic administration to wild type and TLR3-negative mice, and in non-human primates (NHPs) by measuring EZV serum titers, survival extension, and serum liver and kidney function markers. Various doses of aqueous and liposomal poly-ICLC monotherapy provided robust protection in otherwise lethal murine Ebola virus challenge models, when treatment is started on the day of -or one day after virus challenge...
January 3, 2019: Antiviral Research
#36
JOURNAL ARTICLE
Hussein Sultan, Takumi Kumai, Toshihiro Nagato, Juan Wu, Andres M Salazar, Esteban Celis
Vaccines consisting of synthetic peptides representing cytotoxic T-lymphocyte (CTL) epitopes have long been considered as a simple and cost-effective approach to treat cancer. However, the efficacy of these vaccines in the clinic in patients with measurable disease remains questionable. We believe that the poor performance of peptide vaccines is due to their inability to generate sufficiently large CTL responses that are required to have a positive impact against established tumors. Peptide vaccines to elicit CTLs in the clinic have routinely been administered in the same manner as vaccines designed to induce antibody responses: injected subcutaneously and in many instances using Freund's adjuvant...
January 2, 2019: Cancer Immunology, Immunotherapy: CII
#37
JOURNAL ARTICLE
Norbert Hilf, Sabrina Kuttruff-Coqui, Katrin Frenzel, Valesca Bukur, Stefan Stevanović, Cécile Gouttefangeas, Michael Platten, Ghazaleh Tabatabai, Valerie Dutoit, Sjoerd H van der Burg, Per Thor Straten, Francisco Martínez-Ricarte, Berta Ponsati, Hideho Okada, Ulrik Lassen, Arie Admon, Christian H Ottensmeier, Alexander Ulges, Sebastian Kreiter, Andreas von Deimling, Marco Skardelly, Denis Migliorini, Judith R Kroep, Manja Idorn, Jordi Rodon, Jordi Piró, Hans S Poulsen, Bracha Shraibman, Katy McCann, Regina Mendrzyk, Martin Löwer, Monika Stieglbauer, Cedrik M Britten, David Capper, Marij J P Welters, Juan Sahuquillo, Katharina Kiesel, Evelyna Derhovanessian, Elisa Rusch, Lukas Bunse, Colette Song, Sandra Heesch, Claudia Wagner, Alexandra Kemmer-Brück, Jörg Ludwig, John C Castle, Oliver Schoor, Arbel D Tadmor, Edward Green, Jens Fritsche, Miriam Meyer, Nina Pawlowski, Sonja Dorner, Franziska Hoffgaard, Bernhard Rössler, Dominik Maurer, Toni Weinschenk, Carsten Reinhardt, Christoph Huber, Hans-Georg Rammensee, Harpreet Singh-Jasuja, Ugur Sahin, Pierre-Yves Dietrich, Wolfgang Wick
Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors1,2 . For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential3 . There is limited intratumoural infiltration of immune cells4 in glioblastoma and these tumours contain only 30-50 non-synonymous mutations5 . Exploitation of the full repertoire of tumour antigens-that is, both unmutated antigens and neoepitopes-may offer more effective immunotherapies, especially for tumours with a low mutational load...
January 2019: Nature
#38
JOURNAL ARTICLE
Anne-Laure Flamar, Henri Bonnabau, Sandra Zurawski, Christine Lacabaratz, Monica Montes, Laura Richert, Aurelie Wiedemann, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Lauren Hudacik, Andres Salazar, Cécile Peltekian, Rodolphe Thiebaut, Gerard Zurawski, Yves Levy
HIV-1 infection can be controlled by anti-retroviral drug therapy, but this is a lifetime treatment and the virus remains latent and rapidly rebounds if therapy is stopped. HIV-1-infected individuals under this drug regimen have increased rates of cancers, cardiovascular diseases, and autoimmunity due to compromised immunity. A therapeutic vaccine boosting cellular immunity against HIV-1 is therefore desirable and, possibly combined with other immune modulating agents, could obviate the need for long-term drug therapies...
2018: PloS One
#39
JOURNAL ARTICLE
Ajay K Nooka, Michael Luhua Wang, Andrew J Yee, Jonathan L Kaufman, Jooeun Bae, Doris Peterkin, Paul G Richardson, Noopur S Raje
Importance: Increasing evidence suggests the significance of the role of the immune system in the progression of smoldering multiple myeloma (SMM) to symptomatic multiple myeloma (MM). Boosting the immune system via vaccination in the earlier, asymptomatic SMM stage may provide a novel strategy to prevent or slow progression to active MM. Objective: To determine the safety, tolerability, immunogenicity, and anti-MM activity of the PVX-410 multipeptide vaccine with or without lenalidomide...
August 16, 2018: JAMA Oncology
#40
JOURNAL ARTICLE
Chrisann Kyi, Vladimir Roudko, Rachel Sabado, Yvonne Saenger, William Loging, John Mandeli, Tin Htwe Thin, Deborah Lehrer, Michael Donovan, Marshall Posner, Krzysztof Misiukiewicz, Benjamin Greenbaum, Andres Salazar, Philip Friedlander, Nina Bhardwaj
Purpose: Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC), a synthetic double-stranded RNA complex, is a ligand for toll-like receptor-3 and MDA-5 that can activate immune cells, such as dendritic cells, and trigger natural killer cells to kill tumor cells. Patients and Methods: In this pilot study, eligible patients included those with recurrent metastatic disease in whom prior systemic therapy (head and neck squamous cell cancer and melanoma) failed. Patients received 2 treatment cycles, each cycle consisting of 1 mg poly-ICLC 3× weekly intratumorally (IT) for 2 weeks followed by intramuscular (IM) boosters biweekly for 7 weeks, with a 1-week rest period...
October 15, 2018: Clinical Cancer Research
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