Combination comprising immunostimulatory oligonucleotides
The invention relates to a combination and its use for the treatment of diseases. The instant disclosure provides a combination of a so-called T-cell regulator selected from the group comprising PD1, PD-L1, OX40, TIM-3, LAG3, CD137(4-1BB) and a non-coding immunomodulating DNA.
1. A method of treating cancer, comprising administering, to a subject in need thereof, a combination comprising the components of groups (a) and (b):
(a) a first group comprising an antibody binding to at least one of the molecules selected from the group consisting of PD1, PD-L1 and CTLA-4 for affecting their function as T-cell regulators; and
(b) a second group comprising a non-coding sequence of deoxyribonucleic acids comprising at least one sequence motif N 1 N 2 CGN 3 N 4 , wherein N is a nucleotide comprising A, C, T, or G, and C is deoxycytidine, G is deoxyguanosine, A is deoxyadenosine and T is deoxythymidine,
wherein the non-coding sequence of deoxyribonucleic acids is either linear open-chained on both sides, linear open-chained on one side of a double stranded part with a single stranded hairpin on the respective other side of the double strand, or a dumbbell-shaped partially single-stranded covalently closed chain of deoxyribonucleic acids, and
wherein the linear open-chained non-coding sequence of deoxyribonucleic acids comprises at least one nucleotide in L-conformation.
2. The method of claim 1 , wherein the compounds of the combination are administered simultaneously, alternating or successively.
3. The method of claim 1 , wherein said non-coding sequence of deoxyribonucleic acids does not comprise phosphorothioate.