Therapeutic vaccine targeting P-glycoprotein 170 to suppress multidrug resistance in cancer treatment

摘要

Immunogenic composition (A) comprising a vehicle and as antigenic structure, a conjugate (I) of at least one peptide (Ia) derived from extracellular loop 1 of protein P-170, where each (Ia) is associated with several molecules (Ib) of fatty acid of chain length 12-24C is new. Immunogenic composition (A) comprising a vehicle and as antigenic structure, a conjugate (I) of at least one peptide (Ia) derived from extracellular loop 1 of protein P-170, where each (Ia) is associated with several molecules (Ib) of fatty acid of chain length 12-24C is new. (I) displays at least part of the conformation of the loop for inducing anti-P-107 antibodies (Ab) or for causing reversal of multidrug resistance in cancer patients. ACTIVITY : Cytostatic. The tetrapalmitoylated peptide Lys-Gly-Gly-Asn-Met-Thr-Asp-Ser-Phe-Thr-Lys-Ala-Glu-Ala-Ser-Ile-Leu-Pro-Ser-Ile-Thr-Asn-Gln-Gly-Pro-Asn-Ser-Thr-Leu-Ile-Ile-Ser-Asn-Ser-Ser-Leu-(Glu) 3-Gly-Lys-Lys-NH 2 was formulated in liposomes (mole ratio peptide:lipids 1:250) and administered three times to mice at intervals of 2 weeks, at doses of 0.2 ml. The animals were then inoculated (day 0) with1 million P388R chemoresistant cells and treated with 5.5 mg/kg doxorubicin (days 1, 10 and 21) and 2.5 mg/kg vinblastine (days 4 and 14). The mean survival time was 39 days; compare 22 days for animals injected with empty liposomes. MECHANISM OF ACTION : Vaccine; inhibtion of P-170 which is responsible for expulsion of chemotherapeutic agents from cells.