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GFP-REPORTER CONSTRUCTS FOR TUMOR ANTIGEN REGULATION
Phone: (978) 232-1243
Email: IDUNN@CYTOCURE.COM
Phone: (781) 449-8143
Email: MAIL@CYTOCURE.COM
The goals of this Phase I project are to develop stable melanoma cell lines containing a reporter gene linked to the Melan-NMART-1 promoter for use in high throughput drug screening. We propose to
develop these cell lines to identify drugs that up-regulate Melan-A/MART-1
expression. Loss of tumor antigens represents an unmet obstacle to immune-based
therapies (including vaccines). Since T cell recognition relies on both the
expression of tumor antigen target and concomitant presentation of antigen
peptides by HLA molecules, loss of either nominal antigen or the presenting HLA
molecule will prevent T cell-recognition of such tumor variants. We recently
discovered a novel mechanism for the reversible down-regulation of the melanoma
tumor associated antigen, Melan-A/MART-1. Such down-modulation, which we call
"antigen silencing," exemplifies one route by which a tumor can escape immune
destruction in the presence of tumor specific cytotoxic T-cells. We propose to
identify novel drugs that up-regulate Melan-A/MART-1 antigen expression using
reporter cell lines in high throughput screens. Such novel drugs will induce
the maintenance and/or up-regulation of tumor antigen expression necessary to
achieve efficacy in cellular immune-based tumor therapies.
* Information listed above is at the time of submission. *