The Johns Hopkins University

St. Jude Children's Research Hospital

University of South Florida

Whitehead Institute for Biomedical Research

Other

Aduro Biotech Inc.

Drew M Pardoll

Suzanne L Topalian

Bert Vogelstein

Kenneth W Kinzler

Nickolas Papadopoulos

Luis Diaz

Dung Le

Charles George Drake

Jonathan David Powell

Hyam I Levitsky

Juan Fu

Haruo Tsuchiya

Kevin S Gorski

Su-Yi Tseng

Dario A Vignali

Creg J Workman

Elizabeth Marion Jaffee

Ching-Tai Huang

Young Jun Kim

Duojia Pan

Elizabeth A Jaffee

Michael Lim

Fan Pan

Joseph Barbi

Cynthia L Sears

Christine Craig

Kam W Leong

Richard C Mulligan

Richard Jove

Hua Yu

Jonathan Schneck

Henry Brem

Sean O'Herrin

Betty M Tyler

Glenn Dranoff

Rosa V Azhari

Dimitrios Mathios

Edward L Hipkiss

Joseph F Grosso

Derese Getnet

Elizabeth Wick

Tim Greten

Jill Slansky

Audrey Lazenby

Steven A Rosenberg

Thomas W Dubensky, Jr

Jennifer H Elisseeff

Curt I Civin

Stephen B Baylin

Marcin Tomasz Kortylewski

Adam Shultz Adler

William R Bishai

Ivan M Borrello

Meredith Lai Ling Leong

Hong Yu

John R Murphy

Kimberly A Noonan

Laurene Cheung

Cynthia K Bullen

Donald Small

Frank G Guarnieri

J Thomas August

Paul Golumbek

Amit Kumar

Sadiya Parveen

Vijayan Sambasivam

Sumit Siddharth

Dipali Sharma

Ying Zheng

Pankaj Kumar

Andriana Lebid

Meghan Davis

Jing Zeng

Linzhao Cheng

Yan Cui

Katherine Whartenby

Kaitlyn Sadtler

Valentina Hoyos Velez

Benjamin Park

Paul K Golumbe

Jonathan Powell

Katherine A Whartenby

Greg J Workman

Charles C Drake

Xiaoya Pan

Jonathan D Powell

Chung-Tai Huang

The present invention relates to compositions and methods for treating cancer by targeting the Activin signaling pathway. In certain embodiments, combining Activin blockade with immunomodulation alters regulatory T (Treg) cell-mediated immune regulation and treats cancer.

Compositions and methods for targeting activin signaling to treat cancer

The present invention is related to a method of treating or preventing cancer in a subject comprising administering to a subject having cancer or prone of getting cancer a first agent that depletes the subject's regulatory T cells (Tregs); followed by administering to the subject a second agent comprising a checkpoint inhibitor.

Methods of treating or preventing cancer with an agent that depletes tregs and a checkpoint inhibitor

The presently disclosed subject matter provides methods, compositions, and kits for the treatment of cancer using a combination treatment comprising a locally administered chemotherapy and an immunotherapeutic agent. The presently disclosed subject matter also provides methods of promoting the combination treatment and instructing a patient to receive the combination treatment are also provided, as well immunotherapeutic, non-immunosuppressive compositions comprising the combination treatment, and methods of using the immunotherapeutic, non-immunosuppressive compositions for treating cancer.

Combination of immunotherapy with local chemotherapy for the treatment of malignancies

Blockade of immune checkpoints such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) shows promise in patients with cancer. Inhibitory antibodies directed at these receptors have been shown to break immune tolerance and promote anti-tumor immunity. These agents work particularly well in patients with a certain category of tumor. Such tumors may be particularly susceptible to treatment because of the multitude of neoantigens which they produce.

Checkpoint blockade and microsatellite instability

Compositions for the treatment of colorectal cancer target bacterial biofilms in the gastrointestinal tract. Methods of treatment include one or more agents which target bacteria and the bacterial biofilms.

Bacterial biofilms and cancer

Yes-associated protein (Yap), a downstream co-activator of the Hippo pathway, is highly expressed in the Treg cell subset, and is critical to maintain its suppressive activity. Originally discovered in, the Hippo signaling pathway is a major regulator of cellular growth and proliferation in mammals. Loss of Yap expression in Treg cells can lead to superior anti-tumor immune responses, and thus, Yap is an important immunotherapeutic target for cancer.

Inhibition of YAP for breaking tumor immune tolerance

In some embodiments, marrow-infiltrating lymphocytes ('MILs') comprising a chimeric antigen receptor ('CAR') are provided. In some aspects, the embodiments relate to a method for making a recombinant MIL, comprising obtaining bone marrow comprising MILs; and transfecting, transforming, or transducing the MILs with a nucleic acid encoding a chimeric antigen receptor. In some aspects, the embodiments relate to a method for treating a condition in a subject, comprising administering to the subject a MIL comprising a CAR.

Marrow infiltrating lymphocytes (MILs) as a source of T-cells for chimeric antigen receptor (CAR) therapy

The present disclosure relates to compositions and methods for modulating wound healing and regeneration. More particularly, the present disclosure relates to immunomodulatory agents that promote wound healing and tissue regeneration, and that may be optionally used in combination with synthetic or biomaterial scaffolds.

Compositions and methods for modulating wound healing and regeneration

Methods of identifying subjects at increased risk of cancer, based upon detection of biofilms and/or biofilm-associated microbes within a subject, are disclosed. Therapies designed to prevent formation and/or reduce the size of biofilms in a subject identified to be at increased risk of cancer based upon detection of biofilms and/or biofilm-associated microbes are disclosed. In particular embodiments, the invention provides for identification of a subject at elevated risk of developing or having colorectal cancer and/or a colorectal adenoma, based upon detection of a biofilm and/or biofilm-associated bacteria within the gastrointestinal tract of the subject (optionally, within a biopsy specimen and/or stool sample of such subject). Therapies involving administration of an antibiotic agent and/or a probiotic agent to a subject, to prevent or reduce biofilm formation within the gastrointestinal tract of the subject, optionally provided in combination with additional cancer therapy, are also disclosed.

Biofilm formation to define risk for colon cancer

Growing community of inventors

Brookeville, MD, United States of America

Drew M Pardoll