The Brigham and Women's Hospital, Inc.

Dana-farber-cancer Institute Inc.

Tremrx, Inc.

The Cbr Institute for Biomedical Research, Inc.

The Bingham and Women's Hospital

Thomas S Kupper

Wayne A Marasco

Jianhua Sui

Quan Zhu

De-Kuan Chang

Luzheng Lisa Liu

Rachael A Clark

Ulrich Von Andrian

Rahul Purwar

Rachel A Clark

Caroline Robert

Methods of using T cell frequency (TCFR) in melanoma, e.g., as determined by high throughput DNA sequencing of the TCRB gene, as a predictor of disease progression and survival in patients with primary melanoma, and to select and treat subjects.

Methods for identifying progression of a primary melanoma

The present invention comprises a humanized monoclonal antibody that binds to the chemokine receptor CCR4. This antibody is derived from Mab 1567 and recognizes the same epitope. Binding of the invented antibody to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. Moreover, the antibody is used in combination with vaccines to suppress the activity of regulatory T cells.

Humanized monoclonal antibodies and methods of use

Described herein are methods for the treatment of cancer (e.g. melanoma, lung cancer, or other cancers). The methods involve administrating to a subject in need thereof an agonist of the IL-9 receptor (e.g. IL-9), e.g. an agent that binds and activates the IL-9 receptor, or an agent that increases IL-9 expression in the subject (e.g. administration of TH9 cells that express IL-9, or administration of an inhibitor of ROR).

Use of Th9 cells and IL-9 for the treatment of melanoma

The present invention provides affinity matured humanized monoclonal antibodies, bi-specific antibodies, antibody conjugates, and fusion proteins that bind to the chemokine receptor CCR4. This antibody is derived from mAb 1567 and recognizes the same epitope. Binding of the antibodies disclosed herein to CCR4 inhibits ligand-mediated activities and is used to treat symptoms of cancer. Moreover, the antibody is used in combination with vaccines to suppress the activity of regulatory T cells.

Affinity matured anti-CCR4 humanized monoclonal antibodies and methods of use

Attenuated, replication-deficient viruses such as vaccinia viruses are used to deliver an exogenous viral, bacterial, parastic or tumor antigen to an epidermal tissue such as the skin, lungs or gastrointestinal tract, which has been mechanically disrupted, in an amount effective to elicit or stimulate a cell mediated immune response. The epidermis may be mechanically disrupted prior to, at the same time, or immediately after the administration of the vaccine. The vaccine can be used to induce immunity against a pathogen, such as a virus, bacteria, or parasite, or against a cancer in a subject that has or is at risk of developing cancer.

T-cell vaccination with viral vectors via mechanical epidermal disruption

Attenuated, replication-deficient viruses such as vaccinia viruses are used to deliver an exogenous viral, bacterial, parasitic or tumor antigen to an epidermal tissue such as the skin, lungs or gastrointestinal tract, which has been mechanically disrupted, in an amount effective to elicit or stimulate a cell mediated immune response. The epidermal tissue may be mechanically disrupted by a device such as a scarification needle or an abrader device. The epidermis may be mechanically disrupted prior to, at the same time, or immediately after the administration of the vaccine. The vaccine can be used to induce immunity against a pathogen, such as a virus, bacteria, or parasite, or against a cancer in a subject that has or is at risk of developing cancer. In some embodiments a co-stimulatory molecule, a growth factor, an adjuvant and/or a cytokine is administered before, with or after the viral vaccine. In some embodiments, the co-stimulatory molecule is co-expressed with the antigen by the virus.

The present invention is directed to an in vitro method for producing T lymphocytes. The method involves culturing bone marrow cells on a matrix seeded with keratinocytes and fibroblasts.

Process for producing T lymphocytes

The invention provides isolated dendritic cells genetically modified to express a selectin polypeptide, optionally treated with activated platelets or membrane microparticles thereof. The invention also provides isolated platelet modified dendritic cells. Methods for delivering the modified dendritic cells to peripheral lymph nodes and methods for using the modified dendritic cells to stimulate immune responses also are provided. Vaccine compositions containing the modified dendritic cells also are provided.

Growing community of inventors

Weston, MA, United States of America

Thomas S Kupper