New York University

Emmanuelle Godefroy

Nina Bhardwaj

Francine Jotereau

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

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.

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New York, NY, United States of America

Emmanuelle Godefroy