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nina bhardwaj

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
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
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
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
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
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
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
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
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
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
John P Finnigan, Alex Rubinsteyn, Jeffrey Hammerbacher, Nina Bhardwaj
No abstract text is available yet for this article.
December 2015: Oncology (Williston Park, NY)
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
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
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
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
Elizabeth A Miller, Ramya Gopal, Vanessa Valdes, Jeffrey S Berger, Nina Bhardwaj, Meagan P O'Brien
OBJECTIVE: Plasma soluble CD40 ligand (sCD40L) is increased during HIV-1 infection, but it is unknown whether it circulates in monomeric or multimeric forms, and whether the circulating forms have differential effects on myeloid dendritic cell function and adaptive regulation. DESIGN: sCD40L forms were measured in plasma samples from HIV-infected donors. The effects of sCD40L forms on dendritic cell function were measured in vitro. METHODS: To delineate which forms of sCD40L are present in plasma from HIV-infected donors, immunoblots were performed following enrichment of plasma for medium and low-abundance proteins...
July 17, 2015: AIDS
Anne Gallois, Ines Silva, Iman Osman, Nina Bhardwaj
Natural killer (NK) cells are innate immune cells that become progressively exhausted in advanced stage cancer, crippling their ability to execute antitumor functions. We previously characterized the nature of NK cell exhaustion in metastatic melanoma patients, reporting a correlation with high expression of TIM-3. Blockade of this immune checkpoint molecule reversed the exhausted phenotype and improved NK cell function.
December 2014: Oncoimmunology
Rachel Lubong Sabado, Nina Bhardwaj
No abstract text is available yet for this article.
March 19, 2015: Nature
Rachel Lubong Sabado, Anna Pavlick, Sacha Gnjatic, Crystal M Cruz, Isabelita Vengco, Farah Hasan, Meredith Spadaccia, Farbod Darvishian, Luis Chiriboga, Rose Marie Holman, Juliet Escalon, Caroline Muren, Crystal Escano, Ethel Yepes, Dunbar Sharpe, John P Vasilakos, Linda Rolnitzsky, Judith D Goldberg, John Mandeli, Sylvia Adams, Achim Jungbluth, Linda Pan, Ralph Venhaus, Patrick A Ott, Nina Bhardwaj
The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 μg of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle...
March 2015: Cancer Immunology Research
Marina Moskalenko, Michael Pan, Yichun Fu, Ellen H de Moll, Daigo Hashimoto, Arthur Mortha, Marylene Leboeuf, Padmini Jayaraman, Sebastian Bernardo, Andrew G Sikora, Jedd Wolchok, Nina Bhardwaj, Miriam Merad, Yvonne Saenger
We sought to define cellular immune mechanisms of synergy between tumor-antigen-targeted monoclonal antibodies and chemotherapy. Established B16 melanoma in mice was treated with cytotoxic doses of cyclophosphamide in combination with an antibody targeting tyrosinase-related protein 1 (αTRP1), a native melanoma differentiation antigen. We find that Fcγ receptors are required for efficacy, showing that antitumor activity of combination therapy is immune mediated. Rag1(-/-) mice deficient in adaptive immunity are able to clear tumors, and thus innate immunity is sufficient for efficacy...
March 2015: Cancer Immunology Research
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