The Rockefeller University

New York University

Argos Therapeutics, Inc.

Merix Bioscience, Inc.

Nina Bhardwaj

Ralph M Steinman

Gerold Schuler

Robert Darnell

Kayo Inaba

Emmanuelle Godefroy

Matthew Albert

Francine Jotereau

Matthew L Albert

Dusan Bogunovic

David O'Neill

Screening assays and methods of using same for screening to identify modulator agents or compounds that affect matrix metalloproteinase-2 (MMP-2) mediated activation of toll-like receptor-2 (TLR-2) are described herein. Pharmaceutical and immunogenic compositions comprising agents or compounds that modulate MMP-2 mediated activation of TLR-2 are also encompassed. Methods for modulating MMP-2 mediated activation of TLR-2 using MMP-2 peptides in pharmaceutical and immunogenic compositions, as well as vaccines, are also envisioned. Melanoma is an exemplary tumor type that expresses MMP-2 and for which such pharmaceutical and immunogenic compositions, as well as vaccines, would confer benefit to patients. Also encompassed are methods for reducing MMP-2 mediated activation of TLR-2 and downstream signaling therefrom so as to achieve more effective T cell responses to MMP-2 expressing tumors.

Methods, agents and peptides for inhibiting matrix metalloproteinase-2 signaling

Cellular and genetic signatures and methods of using same for subcategorizing stage III melanoma tumors are described herein. The signatures and methods are particularly useful with regard to establishing more distinct criteria on which basis to differentiate stage IIIB and IIIC melanoma patients. Assessment of the cellular and genetic signatures of a melanoma sample using methods described herein yields information on which basis differential survival duration and sensitivity to various cancer therapies can be predicted for a Stage IIIB or Stage IIIC melanoma patients. As described herein, gene expression profiling, determination of mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions may be utilized to predict or assess drug response, drug sensitivity, and clinical outcome in metastatic melanoma patients.

Methods for predicting survival in metastatic melanoma patients

The present invention relates to enhancing, modulating or stimulating the immune response to MMP-2 expressing tumors, including melanoma, and to the modulation and application of immune modulators and MMP-2 peptides for melanoma or other MMP-2 expressing tumor vaccines. The invention provides methods and means to activate an effective response to MMP-2 expressing tumors and modulate the ability of MMP-2 to skew CD4+ T cell responses toward that of T2 cells, which are less effective mediators of tumor cell clearance than T1 cells. Methods and assays are provided for screening for compounds, agents, or peptides capable of enhancing or activating immune responses, particularly to melanoma.

Methods, agents and peptides for inducing an immune response to matrix metalloproteinase-2 expressing tumors

This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing antigen-specific cytotoxic T lymphocytes and T helper cells. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are targeted to dendritic cells by apoptotic cells which may also be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are primed by the apoptotic cells are capable of processing and presenting the processed antigen and inducing cytotoxic T lymphocyte activity or may also be used in vaccine therapies.

Methods for use of apoptotic cells to deliver antigen to dendritic cells for induction or tolerization of T cells

We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or 'priming' phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or 'differentiation' phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derive from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.

Method and compositions for obtaining mature dendritic cells

Methods and compositions for obtaining mature dendritic cells

This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing T antigen specific cytotoxic T lymphocytes. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are provided to dendritic cells using a viral vector such as influenza virus which may be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are infected with the vector are then capable of presenting the antigen and inducing cytotoxic T lymphocyte activity or may also be used as vaccines.

Methods of use of viral vectors to deliver antigen to dendritic cells

We describe an improved method for generating sizable numbers of mature dendritic cells from nonproliferating progenitors in human blood. The first step or &ldquo;priming&rdquo; phase is a culture of T cell depleted mononuclear cells in medium supplemented with GM-CSF and IL-4 to produce immature dendritic cells. The second step or &ldquo;differentiation&rdquo; phase requires the exposure to dendritic cell maturation factor such as monocyte conditioned medium. Using this two-step approach, substantial yields are obtained. The dendritic cells derive from this method have all the features of mature cells. They include a stellate cell shape, nonadherence to plastic, and very strong T cell stimulatory activity. The mature dendritic cells produced according to this invention are useful for activating T cells.

Growing community of inventors

West Orange, NJ, United States of America

Nina Bhardwaj