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Systemic clinical t...
Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination
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- Hammerich, Linda (author)
- Department of Hematology/Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Marron, Thomas U. (author)
- Department of Hematology/Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Upadhyay, Ranjan (author)
- Department of Hematology/Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Svensson-Arvelund, Judit, 1982- (author)
- Department of Hematology/Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Dhainaut, Maxime (author)
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Hussein, Shafinaz (author)
- Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Zhan, Yougen (author)
- Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Ostrowski, Dana (author)
- Department of Hematology/Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Yellin, Michael (author)
- Celldex Therapeutics, Inc., Needham, MA, USA
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Marsh, Henry (author)
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- Salazar, Andres M. (author)
- Oncovir, Inc, Washington, DC, USA
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- Rahman, Adeeb H. (author)
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Brown, Brian D. (author)
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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- Merad, Miriam (author)
- Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 7 Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, York, NY, USA
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- Brody, Joshua D. (author)
- Department of Hematology/Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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(creator_code:org_t)
- 2019-04-08
- 2019
- English.
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In: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 25:5, s. 814-824
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Indolent non-Hodgkin’s lymphomas (iNHLs) are incurable with standard therapy and are poorly responsive to checkpoint blockade. Although lymphoma cells are efficiently killed by primed T cells, in vivo priming of anti-lymphoma T cells has been elusive. Here, we demonstrate that lymphoma cells can directly prime T cells, but in vivo immunity still requires cross-presentation. To address this, we developed an in situ vaccine (ISV), combining Flt3L, radiotherapy, and a TLR3 agonist, which recruited, antigen-loaded and activated intratumoral, cross-presenting dendritic cells (DCs). ISV induced anti-tumor CD8+ T cell responses and systemic (abscopal) cancer remission in patients with advanced stage iNHL in an ongoing trial (NCT01976585). Non-responding patients developed a population of PD1+CD8+ T cells after ISV, and murine tumors became newly responsive to PD1 blockade, prompting a follow-up trial of the combined therapy. Our data substantiate that recruiting and activating intratumoral, cross-priming DCs is achievable and critical to anti-tumor T cell responses and PD1-blockade efficacy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hammerich, Linda
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Marron, Thomas U ...
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Upadhyay, Ranjan
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Svensson-Arvelun ...
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Dhainaut, Maxime
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Hussein, Shafina ...
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Zhan, Yougen
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Ostrowski, Dana
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Yellin, Michael
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Marsh, Henry
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Salazar, Andres ...
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Rahman, Adeeb H.
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Brown, Brian D.
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Merad, Miriam
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Brody, Joshua D.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Nature Medicine
- By the university
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Linköping University