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

摘要

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.

主权项

1. A method for screening to identify a modulator of matrix metalloproteinase protein-2 (MMP-2) mediated activation of toll-like receptor-2 (TLR-2), the method comprising: contacting a composition comprising TLR-2 and MMP-2 with a candidate modulator agent, wherein MMP-2 is a protein comprising or consisting of SEQ ID NO: 1 or a protein at least 90% identical to SEQ ID NO: 1, wherein said protein at 90% identical to SEQ ID NO: 1 activates TLR-2, and measuring direct interaction of TLR-2 and MMP-2 to assess TLR-2/MMP-2 interaction levels in the presence of the candidate modulator agent, wherein detecting a change in TLR-2/MMP-2 interaction levels in the presence of the candidate modulator agent relative to TLR-2/MMP-2 interaction levels in the presence of a control agent identifies a modulator of MMP-2 mediated activation of TLR-2.