The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

The present invention relates to a composition comprising (i) a first substance which is capable to stimulate T cells, (ii) a second substance which is capable to stimulate NK cells (natural killer cells), and (iii) lipopolysaccharide (LPS) and wherein the second substance is a double stranded nucleic acid, single stranded nucleic acid, unmethylated CpG oligodeoxynucleotide, TLR agonist except lipopolysaccharide (LPS), arabinoxylan (BioBran® MGN-3), an immunoglobulin, a murine cytomegalovirus (MCMV)-encoded protein, CCL5 (chemokine (C—C motif) ligand 5), a UL-16-binding protein (ULBP), CD48, CD70, CD155, CD112, Necl-1, B7-H6, ICAM-1, RAE-1 (retinoic acid early inducible 1), 1160, Mult1 and/or hemagglutinin, to a method for measuring, determining and/or detecting the status of cell-mediated immune responsiveness of a subject, to a kit comprising the composition according to the invention, to the use of the composition for measuring, determining and/or detecting of cell-mediated immunity (CMI) and/or for detecting, diagnosing, monitoring an immunosuppression condition in a subject.

The present invention relates to a composition comprising (i) a first substance which is capable to stimulate T cells, (ii) a second substance which is capable to stimulate NK cells (natural killer cells), and (iii) lipopolysaccharide (LPS) and wherein the second substance is a double stranded nucleic acid, single stranded nucleic acid, unmethylated CpG oligodeoxynucleotide, TLR agonist except lipopolysaccharide (LPS), arabinoxylan (BioBran® MGN-3), an immunoglobulin, a murine cytomegalovirus (MCMV)-encoded protein, CCL5 (chemokine (C—C motif) ligand 5), a UL-16-binding protein (ULBP), CD48, CD70, CD155, CD112, Necl-1, B7-H6, ICAM-1, RAE-1 (retinoic acid early inducible 1), 1160, Mult1 and/or hemagglutinin, to a method for measuring, determining and/or detecting the status of cell-mediated immune responsiveness of a subject, to a kit comprising the composition according to the invention, to the use of the composition for measuring, determining and/or detecting of cell-mediated immunity (CMI) and/or for detecting, diagnosing, monitoring an immunosuppression condition in a subject.

Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Disclosed herein is a modified ribonucleotide comprising a nucleoside comprising N4-acetylcytidine and/or 5-hydroxymethyluridine, and polyribonucleotides comprising the same. Also provided herein are compositions comprising a polyribonucleotide of the present disclosure and methods of making and using the same.

Amphiphilic oligonucleotide conjugates that enhance adjuvant function are disclosed. The conjugates typically include: a lipophilic component, and conjugated thereto (directly or indirectly) an immunomodulating oligonucleotide that, if it were not conjugated to the lipophilic component, would suppress TLR7 and/or TLR8 stimulation. In the presence of albumin, these conjugates significantly enhance adjuvant function, in particular the function of TLR7/8-mediated adjuvants such as an imidazoquinolinamine. The conjugates can be administered, along with an adjuvant compound, to a subject in order to cause and/or enhance an immune response (for instance, to an infectious agent or a cancer antigen) in the subject.

Amphiphilic oligonucleotide conjugates that enhance adjuvant function are disclosed. The conjugates typically include: a lipophilic component, and conjugated thereto (directly or indirectly) an immunomodulating oligonucleotide that, if it were not conjugated to the lipophilic component, would suppress TLR7 and/or TLR8 stimulation. In the presence of albumin, these conjugates significantly enhance adjuvant function, in particular the function of TLR7/8-mediated adjuvants such as an imidazoquinolinamine. The conjugates can be administered, along with an adjuvant compound, to a subject in order to cause and/or enhance an immune response (for instance, to an infectious agent or a cancer antigen) in the subject.

Provided herein are antibodies to DC-SIGN, conjugates of DC-SiGN antibodies, and DC-SiGN antibody fusion proteins and the use of such antibodies, conjugates, and fusion proteins for the treatment of diseases such as cancer.

The present invention provides an oligodeoxynucleotide which comprises a CpG oligodeoxynucleotide comprising a nucleotide sequence represented by formula (1):

5′X-CpG-L-CpG-TZ3′  (I) wherein X is T or C, L is a nucleotide sequence consisting of 1 to 7 bases, and Z is T or C, and consisting of 8 to 16 bases, and
a polydeoxyadenylic acid having a length capable of forming a complex with a β-1,3-glucan,
wherein the polydeoxyadenylic acid is linked to the 3′ side of the CpG oligodeoxynucleotide.

In addition, the present invention provides a complex containing said oligodeoxynucleotide and a β-1,3-glucan.