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nina bhardwaj

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https://www.readbyqxmd.com/read/28815047/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#1
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28807052/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#2
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#3
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
August 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28469092/transcriptional-dissection-of-melanoma-identifies-a-high-risk-subtype-underlying-tp53-family-genes-and-epigenome-deregulation
#4
Brateil Badal, Alexander Solovyov, Serena Di Cecilia, Joseph Minhow Chan, Li-Wei Chang, Ramiz Iqbal, Iraz T Aydin, Geena S Rajan, Chen Chen, Franco Abbate, Kshitij S Arora, Antoine Tanne, Stephen B Gruber, Timothy M Johnson, Douglas R Fullen, Leon Raskin, Robert Phelps, Nina Bhardwaj, Emily Bernstein, David T Ting, Georg Brunner, Eric E Schadt, Benjamin D Greenbaum, Julide Tok Celebi
BACKGROUND: Melanoma is a heterogeneous malignancy. We set out to identify the molecular underpinnings of high-risk melanomas, those that are likely to progress rapidly, metastasize, and result in poor outcomes. METHODS: We examined transcriptome changes from benign states to early-, intermediate-, and late-stage tumors using a set of 78 treatment-naive melanocytic tumors consisting of primary melanomas of the skin and benign melanocytic lesions. We utilized a next-generation sequencing platform that enabled a comprehensive analysis of protein-coding and -noncoding RNA transcripts...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28410301/dendritic-cell-strategies-for-eliciting-mutation-derived-tumor-antigen-responses-in-patients
#5
REVIEW
Sreekumar Balan, John Finnigan, Nina Bhardwaj
Dendritic cells (DCs) are equipped for sensing danger signals and capturing, processing, and presenting antigens to naive or effector cells and are critical in inducing humoral and adaptive immunity. Successful vaccinations are those that activate DCs to elicit both cellular and humoral responses, as well as long-lasting memory response against the target of interest. Recently, it has become apparent that tumor cells can provide new sources of antigens through nonsynonymous mutations or frame-shift mutations, leading to potentially hundreds of mutation-derived tumor antigens (MTAs) or neoantigens...
March 2017: Cancer Journal
https://www.readbyqxmd.com/read/28025976/dendritic-cell-based-immunotherapy
#6
REVIEW
Rachel L Sabado, Sreekumar Balan, Nina Bhardwaj
Immunotherapy using dendritic cell (DC)-based vaccination is an approved approach for harnessing the potential of a patient's own immune system to eliminate tumor cells in metastatic hormone-refractory cancer. Overall, although many DC vaccines have been tested in the clinic and proven to be immunogenic, and in some cases associated with clinical outcome, there remains no consensus on how to manufacture DC vaccines. In this review we will discuss what has been learned thus far about human DC biology from clinical studies, and how current approaches to apply DC vaccines in the clinic could be improved to enhance anti-tumor immunity...
January 2017: Cell Research
https://www.readbyqxmd.com/read/27856145/sequence-specific-sensing-of-nucleic-acids
#7
REVIEW
Nicolas Vabret, Nina Bhardwaj, Benjamin D Greenbaum
Innate immune cells are endowed with many nucleic acid receptors, but the role of sequence in the detection of foreign organisms remains unclear. Can sequence patterns influence recognition? In addition, how can we infer those patterns from sequence data? Here, we detail recent computational and experimental evidence associated with sequence-specific sensing. We review the mechanisms underlying the detection and discrimination of foreign sequences from self. We also describe quantitative approaches used to infer the stimulatory capacity of a given pathogen nucleic acid species, and the influence of sequence-specific sensing on host-pathogen coevolution, including endogenous sequences of foreign origin...
January 2017: Trends in Immunology
https://www.readbyqxmd.com/read/27424807/critical-role-for-cd103-cd141-dendritic-cells-bearing-ccr7-for-tumor-antigen-trafficking-and-priming-of-t-cell-immunity-in-melanoma
#8
Edward W Roberts, Miranda L Broz, Mikhail Binnewies, Mark B Headley, Amanda E Nelson, Denise M Wolf, Tsuneyasu Kaisho, Dusan Bogunovic, Nina Bhardwaj, Matthew F Krummel
Intratumoral dendritic cells (DC) bearing CD103 in mice or CD141 in humans drive intratumoral CD8(+) T cell activation. Using multiple strategies, we identified a critical role for these DC in trafficking tumor antigen to lymph nodes (LN), resulting in both direct CD8(+) T cell stimulation and antigen hand-off to resident myeloid cells. These effects all required CCR7. Live imaging demonstrated direct presentation to T cells in LN, and CCR7 loss specifically in these cells resulted in defective LN T cell priming and increased tumor outgrowth...
August 8, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27344341/modulation-of-innate-immunity-in-the-tumor-microenvironment
#9
REVIEW
Elena Gonzalez-Gugel, Mansi Saxena, Nina Bhardwaj
A recent report from the Center for Disease Control identified melanoma as being among the highest causes of cancer-related mortalities in the USA. While interventions such as checkpoint blockade have made substantial impact in terms of improving response rates and overall survival, a significant number of patients fail to respond to treatment or become resistant to therapy. A better understanding of the tumor microenvironment in these patients becomes imperative for identifying immune suppressive mechanisms that impact the development of effective anti-tumor immune responses...
October 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27096321/expansion-and-activation-of-cd103-dendritic-cell-progenitors-at-the-tumor-site-enhances-tumor-responses-to-therapeutic-pd-l1-and-braf-inhibition
#10
Hélène Salmon, Juliana Idoyaga, Adeeb Rahman, Marylène Leboeuf, Romain Remark, Stefan Jordan, Maria Casanova-Acebes, Makhzuna Khudoynazarova, Judith Agudo, Navpreet Tung, Svetoslav Chakarov, Christina Rivera, Brandon Hogstad, Marcus Bosenberg, Daigo Hashimoto, Sacha Gnjatic, Nina Bhardwaj, Anna Karolina Palucka, Brian D Brown, Joshua Brody, Florent Ginhoux, Miriam Merad
Large numbers of melanoma lesions develop resistance to targeted inhibition of mutant BRAF or fail to respond to checkpoint blockade. We explored whether modulation of intratumoral antigen-presenting cells (APCs) could increase responses to these therapies. Using mouse melanoma models, we found that CD103(+) dendritic cells (DCs) were the only APCs transporting intact antigens to the lymph nodes and priming tumor-specific CD8(+) T cells. CD103(+) DCs were required to promote anti-tumoral effects upon blockade of the checkpoint ligand PD-L1; however, PD-L1 inhibition only led to partial responses...
April 19, 2016: Immunity
https://www.readbyqxmd.com/read/27082754/cd4-receptor-is-a-key-determinant-of-divergent-hiv-1-sensing-by-plasmacytoid-dendritic-cells
#11
Meagan O'Brien, Olivier Manches, Craig Wilen, Ramya Gopal, Rumana Huq, Vernon Wu, Nicole Sunseri, Nina Bhardwaj
Plasmacytoid dendritic cells (pDC) are innate immune cells that sense viral nucleic acids through endosomal Toll-like receptor (TLR) 7/9 to produce type I interferon (IFN) and to differentiate into potent antigen presenting cells (APC). Engagement of TLR7/9 in early endosomes appears to trigger the IRF7 pathway for IFN production whereas engagement in lysosomes seems to trigger the NF-κB pathway for maturation into APC. We showed previously that HIV-1 (HIV) localizes predominantly to early endosomes, not lysosomes, and mainly stimulate IRF7 rather than NF-κB signaling pathways in pDC...
April 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27076166/dendritic-cell-vaccines
#12
Rachel Lubong Sabado, Marcia Meseck, Nina Bhardwaj
Exploitation of the patient's own immune system to induce antitumor immune responses using dendritic cell (DC) immunotherapy has been established in early clinical trials as a safe and promising therapeutic approach for cancer. However, their limited success in larger clinical trials highlights the need to optimize DC vaccine preparations. This chapter describes the methodologies utilized for the preparation of the DC vaccine most commonly used in clinical trials. Optional variations at different stages in DC vaccine preparation, based on the nature of antigen, delivery of antigen, maturation stimuli, and mode of administration for DC vaccines, are also presented for consideration as these are often dependent on the disease setting, desired immune response, and/or resources available...
2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27075624/the-human-vaccines-project-a-roadmap-for-cancer-vaccine-development
#13
REVIEW
Pedro Romero, Jacques Banchereau, Nina Bhardwaj, Mark Cockett, Mary L Disis, Glenn Dranoff, Eli Gilboa, Scott A Hammond, Robert Hershberg, Alan J Korman, Pia Kvistborg, Cornelis Melief, Ira Mellman, A Karolina Palucka, Irina Redchenko, Harlan Robins, Federica Sallusto, Theodore Schenkelberg, Stephen Schoenberger, Jeffrey Sosman, Özlem Türeci, Benoît Van den Eynde, Wayne Koff, George Coukos
Cancer vaccine development has been vigorously pursued for 40 years. Immunity to tumor antigens can be elicited by most vaccines tested, but their clinical efficacy remains modest. We argue that a concerted international effort is necessary to understand the human antitumor immune response and achieve clinically effective cancer vaccines.
April 13, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/26981245/immunodynamics-a-cancer-immunotherapy-trials-network-review-of-immune-monitoring-in-immuno-oncology-clinical-trials
#14
REVIEW
Holbrook E Kohrt, Paul C Tumeh, Don Benson, Nina Bhardwaj, Joshua Brody, Silvia Formenti, Bernard A Fox, Jerome Galon, Carl H June, Michael Kalos, Ilan Kirsch, Thomas Kleen, Guido Kroemer, Lewis Lanier, Ron Levy, H Kim Lyerly, Holden Maecker, Aurelien Marabelle, Jos Melenhorst, Jeffrey Miller, Ignacio Melero, Kunle Odunsi, Karolina Palucka, George Peoples, Antoni Ribas, Harlan Robins, William Robinson, Tito Serafini, Paul Sondel, Eric Vivier, Jeff Weber, Jedd Wolchok, Laurence Zitvogel, Mary L Disis, Martin A Cheever
The efficacy of PD-1/PD-L1 targeted therapies in addition to anti-CTLA-4 solidifies immunotherapy as a modality to add to the anticancer arsenal. Despite raising the bar of clinical efficacy, immunologically targeted agents raise new challenges to conventional drug development paradigms by highlighting the limited relevance of assessing standard pharmacokinetics (PK) and pharmacodynamics (PD). Specifically, systemic and intratumoral immune effects have not consistently correlated with standard relationships between systemic dose, toxicity, and efficacy for cytotoxic therapies...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/26860335/in-situ-vaccination-for-the-treatment-of-cancer
#15
REVIEW
Linda Hammerich, Nina Bhardwaj, Holbrook E Kohrt, Joshua D Brody
Vaccination has had a tremendous impact on human health by harnessing the immune system to prevent and eradicate infectious diseases and this same approach might be used in cancer therapy. Cancer vaccine development has been slowed hindered by the paucity of universal tumor-associated antigens and the difficulty in isolating and preparing individualized vaccines ex vivo. Another approach has been to initiate or stimulate an immune response in situ (at the tumor site) and thus exploit the potentially numerous tumor-associated antigens there...
2016: Immunotherapy
https://www.readbyqxmd.com/read/26676902/mutation-derived-tumor-antigens-novel-targets-in-cancer-immunotherapy
#16
REVIEW
John P Finnigan, Alex Rubinsteyn, Jeffrey Hammerbacher, Nina Bhardwaj
No abstract text is available yet for this article.
December 2015: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/26575629/distinguishing-the-immunostimulatory-properties-of-noncoding-rnas-expressed-in-cancer-cells
#17
Antoine Tanne, Luciana R Muniz, Anna Puzio-Kuter, Katerina I Leonova, Andrei V Gudkov, David T Ting, Rémi Monasson, Simona Cocco, Arnold J Levine, Nina Bhardwaj, Benjamin D Greenbaum
Recent studies have demonstrated abundant transcription of a set of noncoding RNAs (ncRNAs) preferentially within tumors as opposed to normal tissue. Using an approach from statistical physics, we quantify global transcriptome-wide motif use for the first time, to our knowledge, in human and murine ncRNAs, determining that most have motif use consistent with the coding genome. However, an outlier subset of tumor-associated ncRNAs, typically of recent evolutionary origin, has motif use that is often indicative of pathogen-associated RNA...
December 8, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26574023/ion-efflux-and-influenza-infection-trigger-nlrp3-inflammasome-signaling-in-human-dendritic-cells
#18
Melissa Victoria Fernandez, Elizabeth Miller, Florian Krammer, Ramya Gopal, Benjamin D Greenbaum, Nina Bhardwaj
The nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome, a multiprotein complex, is an essential intracellular mediator of antiviral immunity. In murine dendritic cells, this complex responds to a wide array of signals, including ion efflux and influenza A virus infection, to activate caspase-1-mediated proteolysis of IL-1β and IL-18 into biologically active cytokines. However, the presence and function of the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome in human dendritic cells, in response to various triggers, including viral infection, has not been defined clearly...
May 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/26429991/aacr-cancer-progress-report-2015
#19
José Baselga, Nina Bhardwaj, Lewis C Cantley, Ronald DeMatteo, Raymond N DuBois, Margaret Foti, Susan M Gapstur, William C Hahn, Lee J Helman, Roy A Jensen, Electra D Paskett, Theodore S Lawrence, Stuart G Lutzker, Eva Szabo
No abstract text is available yet for this article.
October 1, 2015: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26379068/immunization-of-hiv-1-infected-persons-with-autologous-dendritic-cells-transfected-with-mrna-encoding-hiv-1-gag-and-nef-results-of-a-randomized-placebo-controlled-clinical-trial
#20
RANDOMIZED CONTROLLED TRIAL
Rajesh T Gandhi, Douglas S Kwon, Eric A Macklin, Janet R Shopis, Anna P McLean, Nicole McBrine, Theresa Flynn, Lauren Peter, Amy Sbrolla, Daniel E Kaufmann, Filippos Porichis, Bruce D Walker, Nina Bhardwaj, Dan H Barouch, Daniel G Kavanagh
BACKGROUND: HIV-1 eradication may require reactivation of latent virus along with stimulation of HIV-1-specific immune responses to clear infected cells. Immunization with autologous dendritic cells (DCs) transfected with viral mRNA is a promising strategy for eliciting HIV-1-specific immune responses. We performed a randomized controlled clinical trial to evaluate the immunogenicity of this approach in HIV-1-infected persons on antiretroviral therapy. METHODS: Fifteen participants were randomized 2:1 to receive intradermal immunization with HIV-1 Gag- and Nef-transfected DCs (vaccine) or mock-transfected DCs (placebo) at weeks 0, 2, 6, and 10...
March 1, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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