The present invention provides a medicine containing a Toll-like receptor agonist, LAG-3 protein, a variant or derivative thereof.

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.

Polynucleotide constructs are disclosed, that are potent activators of a STING-independent DNA sensing pathway (SIDSP), in which the DNA damage response protein DNA-PK is the sensor of the SIDSP, along with tire heat shock protein HSPA8 as a unique SIDSP target. The polynucleotide constructs of the disclosure are also potent activators of the cGAS-STING DNA sensing pathway. These pathways arm key components of the innate immune response that is important for antiviral immunity, contributes to specific autoimmune diseases, and mediate important aspects of antitumor immunity.

Polynucleotide constructs are disclosed, that are potent activators of a STING-independent DNA sensing pathway (SIDSP), in which the DNA damage response protein DNA-PK is the sensor of the SIDSP, along with tire heat shock protein HSPA8 as a unique SIDSP target. The polynucleotide constructs of the disclosure are also potent activators of the cGAS-STING DNA sensing pathway. These pathways arm key components of the innate immune response that is important for antiviral immunity, contributes to specific autoimmune diseases, and mediate important aspects of antitumor immunity.

Disclosed herein are compositions and methods for inhibiting the growth of cells or inducing cell death. The composition capable of inhibiting the growth of cells or inducing cell death comprises a 5′-triphosphate non-linear RNA. The RNA comprises a first stem-loop formed from the complete or partial hybridization of at least 8 nucleotide pairings and may optionally comprise a second stem-loop formed from the complete or partial hybridization of at least 8 nucleotide pairings and a spacer between the first stem-loop and the second stem loop. Methods for inhibiting the growth of cells or inducing cell death comprise contacting cells with the composition or administering the composition to a subject in an amount effective to inhibit the growth of the cells or induce death of the cells.

Disclosed herein are compositions and methods for inhibiting the growth of cells or inducing cell death. The composition capable of inhibiting the growth of cells or inducing cell death comprises a 5′-triphosphate non-linear RNA. The RNA comprises a first stem-loop formed from the complete or partial hybridization of at least 8 nucleotide pairings and may optionally comprise a second stem-loop formed from the complete or partial hybridization of at least 8 nucleotide pairings and a spacer between the first stem-loop and the second stem loop. Methods for inhibiting the growth of cells or inducing cell death comprise contacting cells with the composition or administering the composition to a subject in an amount effective to inhibit the growth of the cells or induce death of the cells.

This disclosure provides intact bacterially derived minicells containing nucleic acids adjuvants or plasmids encoding nucleic acids adjuvants that can produce a desired immune response in target cells. This disclosure further provides methods that employ minicells to deliver nucleic acids adjuvants for use in the treatment of diseases, including neoplastic disease and cancer.

This disclosure provides intact bacterially derived minicells containing nucleic acids adjuvants or plasmids encoding nucleic acids adjuvants that can produce a desired immune response in target cells. This disclosure further provides methods that employ minicells to deliver nucleic acids adjuvants for use in the treatment of diseases, including neoplastic disease and cancer.

A nucleic acid-drug complex is provided in the present disclosure, which includes a nucleic acid sequence of an anti-PD-L1 aptamer and a CpG oligonucleotide sequence capable of activating TLR9, in which the CpG oligonucleotide sequence consists of a first fragment and a second fragment, and the nucleic acid sequence of the anti-PD-L1 aptamer is inserted between the first fragment and the second fragment.