Institution
Ragon Institute of MGH, MIT and Harvard
Healthcare•Cambridge, Massachusetts, United States•
About: Ragon Institute of MGH, MIT and Harvard is a healthcare organization based out in Cambridge, Massachusetts, United States. It is known for research contribution in the topics: Immune system & Antibody. The organization has 858 authors who have published 1397 publications receiving 82294 citations. The organization is also known as: Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University & Phillip T. and Susan M. Ragon Institute.
Topics: Immune system, Antibody, T cell, Cytotoxic T cell, Antigen
Papers
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TL;DR: Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together.
5,506 citations
01 May 2015
TL;DR: Drop-seq as discussed by the authors analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts' cell of origin, and identifies 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes.
Abstract: Cells, the basic units of biological structure and function, vary broadly in type and state. Single-cell genomics can characterize cell identity and function, but limitations of ease and scale have prevented its broad application. Here we describe Drop-seq, a strategy for quickly profiling thousands of individual cells by separating them into nanoliter-sized aqueous droplets, associating a different barcode with each cell's RNAs, and sequencing them all together. Drop-seq analyzes mRNA transcripts from thousands of individual cells simultaneously while remembering transcripts' cell of origin. We analyzed transcriptomes from 44,808 mouse retinal cells and identified 39 transcriptionally distinct cell populations, creating a molecular atlas of gene expression for known retinal cell classes and novel candidate cell subtypes. Drop-seq will accelerate biological discovery by enabling routine transcriptional profiling at single-cell resolution. VIDEO ABSTRACT.
3,365 citations
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TL;DR: The feasibility, safety, and immunogenicity of a vaccine that targets up to 20 predicted personal tumour neoantigens is demonstrated and a strong rationale for further development of this approach, alone and in combination with checkpoint blockade or other immunotherapies is provided.
Abstract: Effective anti-tumour immunity in humans has been associated with the presence of T cells directed at cancer neoantigens, a class of HLA-bound peptides that arise from tumour-specific mutations. They are highly immunogenic because they are not present in normal tissues and hence bypass central thymic tolerance. Although neoantigens were long-envisioned as optimal targets for an anti-tumour immune response, their systematic discovery and evaluation only became feasible with the recent availability of massively parallel sequencing for detection of all coding mutations within tumours, and of machine learning approaches to reliably predict those mutated peptides with high-affinity binding of autologous human leukocyte antigen (HLA) molecules. We hypothesized that vaccination with neoantigens can both expand pre-existing neoantigen-specific T-cell populations and induce a broader repertoire of new T-cell specificities in cancer patients, tipping the intra-tumoural balance in favour of enhanced tumour control. Here we demonstrate the feasibility, safety, and immunogenicity of a vaccine that targets up to 20 predicted personal tumour neoantigens. Vaccine-induced polyfunctional CD4+ and CD8+ T cells targeted 58 (60%) and 15 (16%) of the 97 unique neoantigens used across patients, respectively. These T cells discriminated mutated from wild-type antigens, and in some cases directly recognized autologous tumour. Of six vaccinated patients, four had no recurrence at 25 months after vaccination, while two with recurrent disease were subsequently treated with anti-PD-1 (anti-programmed cell death-1) therapy and experienced complete tumour regression, with expansion of the repertoire of neoantigen-specific T cells. These data provide a strong rationale for further development of this approach, alone and in combination with checkpoint blockade or other immunotherapies.
1,921 citations
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University of KwaZulu-Natal1, University of Massachusetts Medical School2, Ragon Institute of MGH, MIT and Harvard3, Harvard University4, Broad Institute5, Massachusetts Institute of Technology6, Boston Children's Hospital7, Aix-Marseille University8, Centre national de la recherche scientifique9, Vanderbilt University Medical Center10, Brigham and Women's Hospital11, University of California, Berkeley12, University of Washington13, Fred Hutchinson Cancer Research Center14, Seattle Children's15, University of Pittsburgh16, University of Sheffield17, United States Department of Veterans Affairs18, University College London19, Scripps Research Institute20
TL;DR: The data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection.
1,911 citations
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TL;DR: Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes.
Abstract: Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine.
1,473 citations
Authors
Showing all 870 results
Name | H-index | Papers | Citations |
---|---|---|---|
Dennis R. Burton | 164 | 683 | 90959 |
Bruce D. Walker | 155 | 779 | 86020 |
Joseph Sodroski | 138 | 542 | 77070 |
Laurie H. Glimcher | 135 | 466 | 68983 |
Gary J. Nabel | 133 | 497 | 58611 |
Douglas A. Lauffenburger | 122 | 705 | 55326 |
Ulrich H. von Andrian | 115 | 269 | 46535 |
Mark A. Kay | 108 | 388 | 45846 |
Mary Carrington | 107 | 414 | 46962 |
Amalio Telenti | 102 | 421 | 40509 |
Raymond T. Chung | 98 | 729 | 37207 |
David R. Bangsberg | 97 | 463 | 39251 |
Darrell J. Irvine | 93 | 363 | 26958 |
Dan H. Barouch | 92 | 447 | 35945 |
Nir Hacohen | 91 | 319 | 58903 |