Additional information concerning the inventions is available upon request.
The four inventions described below are assigned to the National Institutes of Health, have been filed in the United States Patent and Trademark Office, and are available for licensing in the United States. A signed Confidential Disclosure Agreement is required to receive a copy of any patent application. The resulting hetero-oligomeric complex is internalized by endocytosis and acidification of the vesicle causes insertion of the PA63 heptamer into the endosomal membrane to produce a channel through which LF or EF translocate to the cytosol, where LF or EF induce cytotoxic events. These MMP or plasminogen activator targeted PA mutants are only activated by plasminogen activator or MMP-expressing tumor cells so as to specifically deliver a toxin or a therapeutic agent. This is important because a wide variety of tumor cell lines and tissues overexpress MMPs or plasminogen activators, and this overexpression is highly correlated to tumor invasion and metastasis.