Methods and products for enhancing immune responses using imidazoquinoline compounds

A method of inducing an immune response in a subject against an antigen, the method comprising

• administering a composition comprising an imidazoquinoline agent, wherein the imidazoquinoline agent induces TLR8-mediated signal transduction, to a subject via a route of administration selected from the group consisting of mucosal, oral, intranasal, intratracheal, ocular, vaginal, rectal, buccal, and by inhalation, wherein the composition further comprises an antigen, in an effective amount to induce an immune response to the antigen.

A method of inducing an immune response in a subject against an antigen, the method comprising

• administering a composition comprising an imidazoquinoline agent, wherein the imidazoquinoline agent is selected from the group consisting of an imidazoquinoline amine, an imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused cycloalkylimidazopyridine amine, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (R-837), and 4-amino-α,α-dimethyl-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ethanol (R-848), to a subject via a route of administration selected from the group consisting of mucosal, oral, intranasal, intratracheal, ocular, vaginal, rectal, buccal, and by inhalation, wherein the composition further comprises an antigen, in an effective amount to induce an immune response to the antigen.

A method of enhancing an immune response to a cancer vaccine in a subject, the method comprising

• administering a composition comprising an imidazoquinoline agent to a subject via a route of administration selected from the group consisting of mucosal, oral, intranasal, intratracheal, ocular, vaginal, rectal, buccal, and by inhalation, wherein the composition further comprises a cancer vaccine, wherein the composition comprises an effective amount of the imidazoquinoline agent to enhance an immune response to the cancer vaccine, wherein the imidazoquinoline agent is selected from the group consisting of an imidazoquinoline amine, an imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused cycloalkylimidazopyridine amine, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (R-837), and 4-amino-α,α-dimethyl-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ethanol (R-848).

A method of enhancing an immune response to a cancer vaccine in a subject, the method comprising

• administering a composition comprising an imidazoquinoline agent to a subject via a route of administration selected from the group consisting of mucosal, oral, intranasal, intratracheal, ocular, vaginal, rectal, buccal, and by inhalation, wherein the composition further comprises a cancer vaccine, wherein the composition comprises an effective amount of the imidazoquinoline agent to enhance an immune response to the cancer vaccine.

A pharmaceutical composition comprising an antigen and an imidazoquinoline agent, wherein the imidazoquinoline agent is an imidazoquinoline agent that induces TLR8-mediated signal transduction, or a pharmaceutically acceptable form thereof, formulated for administration by a route selected from the group consisting of mucosal, oral, intranasal, intratracheal, ocular, vaginal, rectal, buccal, and by inhalation.

A pharmaceutical composition comprising an antigen and an imidazoquinoline agent, wherein the imidazoquinoline agent is selected from the group consisting of an imidazoquinoline amine, an imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused cycloalkylimidazopyridine amine, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (R-837), and 4-amino-α,α-dimethyl-2-ethoxymethyl-1H-imidazo[4,5-c]quinolin-1-ethanol (R-848), or a pharmaceutically acceptable form or any of the foregoing, formulated for administration by a route selected from the group consisting of mucosal, oral, intranasal, intratracheal, ocular, vaginal, rectal, buccal, and by inhalation.

A kit comprising a sustained release vehicle comprising an imidazoquinoline agent and a container housing an antigen and instructions for timing of administration of the compounds.

A method of generating an immune response in a subject against an antigen, the method comprising:

• topically administering a TLR8 agonist IRM compound to an administration site of the subject in an amount effective to potentiate an immune response to an antigen;
• and administering at the administration site a pharmaceutical composition comprising the antigen in an amount effective to generate an immune response to the antigen.

A method of generating an immune response in a subject against an antigen, the method comprising:

• topically administering an IRM compound to an administration site of the subject in an amount effective to potentiate an immune response to an antigen;
• and administering at the administration site a pharmaceutical composition comprising the antigen in an amount effective to generate an immune response to the antigen.;
• wherein the lkM compound is a substituted imidazoquinoline amine, tetrahydroimidazoquinoline amine, an imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused cycloalkylimidazopyridine amine, an imidazonaphthyridine amine, a tetrahydroimidazonaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine.

A method of increasing an immune response raised by a subject in response to administering a vaccine at a vaccination site, the method comprising topically administering an IRM compound to the subject at the vaccination site in an amount effective to increase the immune response to the vaccine, wherein the IRM compound is a substituted imidazoquinoline amine, tetrahydroimidazoquinoline amine, an imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused cycloalkylimidazopyridine amine, an imidazonaphthyridine amine, a tetrahydroimidazonaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, or a thiazolonaphthyridine amine.

A method of increasing an immune response raised by a subject in response to administering a vaccine at a vaccination site, the method comprising topically administering a TLR8 agonist IRM compound to the subject at the vaccination site in an amount effective to increase the immune response to the vaccine.

A pharmaceutical combination comprising:

• a component that comprises an antigen;
• and a topical formulation that comprises TLR8 agonist, or a pharmaceutically acceptable form thereof.

A pharmaceutical combination comprising:

• a component that comprises an antigen;
• and a topical formulation that comprises an IRM compound selected from the group consisting of a tetrahydroimidazoquinoline amine, an imidazopyridine amine, a 1,2-bridged imidazoquinoline amine, a 6,7-fused cycloalkylimidazopyridine amine, an imidazonaphthyridine amine, a tetrahydroimidazonaphthyridine amine, an oxazoloquinoline amine, a thiazoloquinoline amine, an oxazolopyridine amine, a thiazolopyridine amine, an oxazolonaphthyridine amine, a thiazolonaphthyridine amine, a substituted imidazoquinoline amine, or a pharmaceutically acceptable form of any of the foregoing.

A kit comprising:

• a first container that contains a pharmaceutical composition that includes an antigen;
• and a second container that includes an IRM compound, or a pharmaceutically acceptable form thereof.