The Brigham and Women's Hospital, Inc.

Brandeis University

National Institutes of Health, a Component of the US Dept. of Health & Human Services

Other

Biogen Ma Inc.

Syntimmune, Inc.

Harvard College

Richard S Blumberg

Neil E Simister

Wayne I Lencer

Kristi Baker

Timo Rath

Kevin McDonnell

Adam Robert Mezo

Zachary R Taylor

Warren Strober

Ivan J Fuss

Arron Hearn

Susan Dana Jones

Frank Heller

Rosa Maria Silva Garcia Grenha

Yu-Hwa Huang

Timothy Gareth Jones

Robert George Edward Holgate

Derry Roopenian

Laurence J Blumberg

Amit Gandhi

Dennis L Kasper

Vijay K Kuchroo

Ana Carrizosa Anderson

Nalan Utku

Chen Zhu

Robert George E Holgate

Monica Bertagnolli

Sungwhan Oh

Dingding An

Wayne L Lencer

Charles Yoon

Joana F Neves

Michal Pyzik

Arthur Kaser

Torsten Olszak

Timothy T C Kuo

Shankar S Iyer

Amit Ghandi

Amadeu Llebaria

Timothy David Jones

Joana Pereira Das Neves

Provided herein are recombinant antibodies and antigen-binding fragments thereof useful for binding to and inhibiting carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1). Also provided are methods of using the disclosed CEACAM1 antibodies and antigen-binding fragments thereof for reducing T-cell tolerance and for the treatment of cancer.

Humanized and affinity-matured anti-CEACAM1 antibodies

As demonstrated herein, soluble human FcRn binds to AFP with affinities greater than observed with albumin, and is able to interfere with FcRn-mediated protection of and functional associations with IgG. Accordingly, provided herein, in some aspects, are compositions and methods to inhibit FcRn and AFP interactions in diseases or disorders where elevated AFP levels are associated with immunosuppression. Also provided herein, in some aspects, are compositions and methods to enhance or potentiate FcRn and AFP interactions in diseases or disorders with decreased AFP levels or diseases or disorders where increasing AFP levels increasing with immunosuppression.

Methods to manipulate alpha-fetoprotein (AFP)

Provided herein are methods and compositions related to a method of stimulating the immune system in a subject in need thereof by administering an agent that increases the level or activity of indoleamine 2,3-dioxygenase (IDO1) and/or aryl hydrocarbon receptor (Ahr).

Oxazole containing compounds as activators of IDO1 and AhR

Provided herein are recombinant antibodies and antigen-binding portions thereof useful for binding to FcRn and blocking binding of FcRn to human serum albumin. The FcRn-binding proteins can be used to treat a variety of disorders including acute and chronic toxic exposure.

Humanized affinity matured anti-FcRn antibodies

Provided herein are recombinant antibodies and antigen-binding portions thereof useful for binding to FcRn and blocking binding of FcRn to IgG Fc. The FcRn-binding proteins can be used to treat a variety of disorders including autoimmune disorders.

The invention provided herein includes isolated polypeptides that specifically block the interaction between neonatal Fc receptor (FcRn) and albumin. Blocking the interaction treats diseases and conditions caused by increased amounts of albumin or modified albumin that possesses pathogenic properties wherein it is deemed desirable to decrease albumin levels. Accordingly, also provided are methods of using these isolated polypeptides to treat various diseases and conditions caused by increased amounts of albumin or modified albumin that possesses pathogenic properties. The invention provided herein also includes isolated polypeptides capable of binding to a non-IgG and non-albumin competitive site on an FcRn alpha 3 domain. These can be useful for tracking FcRn without inhibiting IgG or albumin binding or function. Accordingly, the invention also includes methods and systems to track FcRn without inhibiting IgG or albumin binding or function.

FC receptor (FcRn) binding peptides and uses thereof

Described herein are compositions and methods for the modulation of T-cell tolerance, which can be upregulated or down regulated by concurrent enhancement or inhibition of CEACAM1/TIM3 interactions. As described herein, the discovery that CEACAM1 is a direct ligand of TIM3 and vice versa has been shown in cis and in trans. In addition, as demonstrated herein, CEACAM1 and TIM3 are co-regulated during the course of T-cell activation.

Modulation of the immune response

The invention provides, inter alia, immunoinhibitory glycosphingolipids and immunoinhibitory alpha-galactosylceramides and compositions and preparations thereof, and methods of use thereof including in the treatment of conditions characterized by increased iNKT cells and/or activity.

Glycosphingolipids and methods of use thereof

Described herein are compositions for increasing IL-12 production comprising IgG or a fragment thereof or a variant thereof and uses of said compositions for treating cancer and infectious diseases. Also described herein are compositions for decreasing IL-12 production comprising an agent that inhibits signaling mediated by interaction between FcRn and IgG and uses of said compositions for treating autoimmune diseases. Further described herein are methods for assessing efficacy of treatment by monitoring levels of various cytokines in the subject.

Compositions and methods for modulating an immune response

Provided herein are MiIP-Seq assays and methods for detecting and/or identifying an immune-stimulating microbe in a patient sample. Also provided herein are methods for diagnosing an infectious disease or identifying a previously uncharacterized microbe in a patient sample. The methods and assays described herein are advantageous over existing methods in that they (i) do not require a culture step for microbe expansion, (ii) are not specific for a particular microbe and can be used to identify a previously uncharacterized microbe, and (iii) permits rapid processing due to the lack of a microbe culture step.

Assays and methods to sequence microbes directly from immune complexes

Provided herein are recombinant monoclonal antibodies and antigen-binding portions thereof useful in inhibiting CEACAM1 in tumor cells, and methods of their use in anti-tumor proliferation and invasiveness therapies, such as the treatment of cancer, particularly pancreatic cancer.

Anti-CEACAM1 recombinant antibodies for cancer therapy

Method of treating or preventing the inflammatory response of colitis in a subject comprising administering to the subject an effective amount of a substance that modulates IL-13 activity (FIG.). The invention also provides a method of treating or preventing the inflammatory response of colitis in a subject comprising administering to the subject an effective amount of a substance that modulates NK-T cell activity. The invention also provides for the screening of substances that treat or prevent the inflammatory response of colitis.

Methods of treating and preventing colitis involving IL-13 and NK-T cells

Provided herein are, inter alia, methods for identifying a candidate compound for treating the toxic effects of compounds or molecules that bind to albumin in a subject. The methods include identifying test compounds that inhibit the binding between FcRn and albumin.

Disrupting FCRN-albumin interactions

Growing community of inventors

Waltham, MA, United States of America

Richard S Blumberg