St. Jude Children's Research Hospital

Johns Hopkins University

Dario A Vignali

Creg J Workman

Drew M Pardoll

Jonathan David Powell

Charles George Drake

Ching-Tai Huang

Lauren Collison

Kate Vignali

Jonathan Powell

Greg J Workman

Charles C Drake

Chung-Tai Huang

Combinations of anti-cancer antibodies and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.

Methods of increasing T cell immune response in the treatment of cancer

Anti-CD223 antibodies overcome immune suppression in cancer patients. The anti-CD223 antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.

Methods for treatment comprising an antibody that binds CD223 protein

Methods for regulating T cell function in a subject, particularly regulatory T cell activity are provided. Methods of the invention include administering to a subject a therapeutically effective amount of an Interleukin 35-specific binding agent, such as an antibody or small molecule inhibitor. The invention further provides methods for enhancing the immunogenicity of a vaccine or overcoming a suppressed immune response to a vaccine in a subject, including administering to the subject a therapeutically effective amount of an IL35-specific binding agent and administering to the subject a vaccine. In one embodiment the vaccine is a cancer vaccine.

Monoclonal antibodies to interleukin 35 and methods of use thereof to inhibit regulatory T cell function

T effector cells modulated via interleukin 35 and methods of culturing same

Mammals with cancer are treated with an antibody which specifically binds to CD223 protein and inhibits negative T cell regulatory function of CD223. The mammal may be a human. The antibody may be a monoclonal antibody. The amount of the antibody administered may be sufficient to enhance an immune T cell response to the cancer.

Method for treating cancer with an antibody to CD223 protein

Method of inhibiting regulatory T-cell activity by administering an antibody that inhibits interleukin 35

Regulatory T cells (Treg) limit autoimmunity but can also attenuate the magnitude of anti-pathogen and anti-tumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Treg in vivo requires identification of Treg selective receptors. A comparative analysis of gene expression arrays from antigen specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg selective expression of LAG-3 (CD223), a CD4-related molecule that binds MHC class II. LAG-3 expression on CD4+ T cells correlates with the cells' in vitro suppressor activity, and ectopic expression of LAG-3 on CD4 T cells confers suppressor activity on the T cells. Antibodies to LAG-3 inhibit suppression both in vitro and in vivo. LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

Anti-cancer vaccine composition comprising an anti-CD223 antibody and kit comprising an anti-cancer vaccine and an anti-CD223 antibody

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Pittsburgh, PA, United States of America

Dario A Vignali