Amphipathic lytic peptides are ideally suited to use in a ligand / cytotoxin combination to specifically inhibit cells that are driven by or are dependent upon a specific ligand interaction; for example, to induce
sterility or long-term contraception, or to
attack tumor cells, or to selectively lyse virally-infected cells, or to
attack lymphocytes responsible for autoimmune diseases. The peptides act directly on
cell membranes, and need not be internalized. Administering a combination of
gonadotropin-releasing
hormone (GnRH) (or a GnRH
agonist) and a membrane-active
lytic peptide produces long-term contraception or sterilization in animals
in vivo. Administering
in vivo a combination of a ligand and a membrane-active
lytic peptide kills cells with a
receptor for the ligand. The compounds are relatively small, and are not antigenic.
Lysis of gonadotropes has been observed to be very rapid (on the order of ten minutes.)
Lysis of
tumor cells is rapid. The two components-the ligand and the
lytic peptide-may optionally be administered as a
fusion peptide, or they may be administered separately, with the ligand administered slightly before the lytic
peptide, to activate cells with receptors for the ligand, and thereby make those cells susceptible to
lysis by the lytic
peptide. The compounds may be used in
gene therapy to treat malignant or non-malignant tumors, and other diseases caused by clones or populations of "normal" host cells bearing specific receptors (such as lymphocytes), because genes encoding a lytic
peptide or encoding a lytic peptide /
peptide hormone fusion may readily be inserted into hematopoietic stem cells or myeloid precursor cells.