We have demonstrated that conjugates of lytic peptides and a 15 amino acid segment of CG cause regression of primary tumors and destruction of metastatic cells of human breast, prostate, and ovarian cell xenografts. One of these conjugates, Phor21-βCG(ala) is effective at very low concentrations (0.008 mg/kg). A conjugate of LHRH and a lytic peptide (Hecate) also proved effective in regressing prostate cancer xenografts.
The ability of the lytic peptide-βCG and LHRH-lytic peptide compounds to destroy primary tumors and high percentages of metastatic cells in all peripheral tissues and organs tested suggests that these compounds may prove most useful in treating patients whose tumors express sufficient numbers of LH/CG or LHRH receptors. The lytic peptide conjugates may prove particularly useful in inhibiting the development of metastases after surgery to remove the primary tumor.
Phor14-βCG(ala) and Hecate-βCG have half lives of about 1 hr and are almost completely eliminated from the circulation at 4 hr after injection (unpublished data). This property, along with the relatively small size of the molecules, contributes to the low antigenicity of these compounds. Since, they act at the level of the cell membrane, the lytic peptide conjugates are not subject to the multiple drug rejection (MDR) phenomenon.
|
