Immune modulating oligonucleotides in connection with chemotherapeutic measures
View Patent ↗The invention relates to the use of immune modulators on the basis of DNA in the form of covalently closed nucleic acid molecules comprising immune stimulatory sequence motifs, for the production of a pharmaceutical for the therapeutic treatment of tumor diseases in combination with chemotherapeutic drugs.
1. A method for treating a human patient with a tumor comprising
administering to said patient an immune modulator in an amount effective for generating a specific immune response against tumor antigens; and
subsequently administering radiotherapy to said patient,
wherein said tumor antigens are liberated by the radiotherapy, and
wherein said immune modulator comprises a circular single strand of deoxyribonucleic acid of 40 to 200 nucleotides with a partially complementary antiparallel base sequence, said partial complementarity providing a dumbbell-shaped molecule, and
wherein said immune modulator comprises the sequence N 1 N 2 CGN 3 N 4 within both of the loop portions of the dumbbell-shaped molecule, wherein N 1 N 2 is GT, GG, GA, AT or AA and N 3 N 4 is CT or TT, and wherein C is deoxycytosine, G is deoxyguanosine, A is deoxyadenosine and T is deoxythymidine.
2. A method for treating a human patient with a tumor comprising
administering to said patient an immune modulator in an amount effective for generating a specific immune response against tumor antigens; and
subsequently administering chemotherapy to said patient,
wherein said tumor antigens are liberated by the chemotherapy, and
wherein said immune modulator comprises a circular single strand of deoxyribonucleic acid of 40 to 200 nucleotides having a partially complementary antiparallel base sequence, said partial complementarity providing a dumbbell-shaped molecule, and
wherein said immune modulator comprises the sequence N 1 N 2 CGN 3 N 4 within both of the loop portions of the dumbbell-shaped molecule, wherein N 1 N 2 is GT, GG, GA, AT or AA and N 3 N 4 is CT or TT, and wherein C is deoxycytosine, G is deoxyguanosine, A is deoxyadenosine and T is deoxythymidine.
3. The method of claim 2 further comprising administering the immune modulator after the chemotherapy.
4. The method of claim 2 wherein the chemotherapy comprises treatment with a topoisomerase inhibitor, an alkylating agent, a platin compound, an antimetabolite, an anthracycline, an actinomycin, a vinca alkaloid, a taxane, an anti-estrogen or combinations thereof.
5. The method of claim 1 or 2 wherein the immune modulator is administered intradermally, subcutaneously or intramuscularly.
6. The method of claim 1 or 2 wherein the immune modulator is administered as two injections of 0.5 mg on the same day, and the administration is repeated at intervals between two and eight days.
7. The method of claim 1 wherein said patient receives a cumulative total of 1 mg to 10 mg of the immune modulator prior to receiving radiotherapy.
8. The method of claim 2 wherein said patient receives a cumulative total of 1 mg to 10 mg of the immune modulator prior to receiving chemotherapy.