Methods and compositions for generating an immune response by inducing cd40 and pattern recognition receptors and adaptors thereof
OwnerDavid Spencer, Natalia Leptevainventors
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Abstract
Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing pattern recognition receptor activity, and CD40 activity. Also provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing CD40 activity without prostaglandin E2. Also provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible chimeric molecule comprising a region of a pattern recognition receptor or an adaptor thereof.
Claims40
1-39. (canceled)
A method for activating an antigen-presenting cell, which comprises:
- a. transducing an antigen-presenting cell with a nucleic acid having a nucleotide sequence that encodes a chimeric protein, wherein the chimeric protein comprises a membrane targeting region, a ligand-binding region and a CD40 cytoplasmic polypeptide region lacking the CD40 extracellular domain;
- b. contacting the antigen-presenting cell with a non-protein multimeric ligand that binds to the ligand-binding region;
- and
- c. contacting the antigen-presenting cell with a Pattern Recognition Receptor (PRR) ligand, whereby the antigen-presenting cell is activated.
A method for activating an antigen-presenting cell, which comprises:
- a. transducing an antigen-presenting cell with a nucleic acid having a nucleotide sequence that encodes a chimeric protein, wherein the chimeric protein comprises a membrane targeting region, a ligand-binding region and a CD40 cytoplasmic polypeptide region lacking the CD40 extracellular domain;
- and
- b. contacting the antigen-presenting cell with a non-protein multimeric ligand that binds to the ligand-binding region, wherein the antigen-presenting cell is not contacted with prostaglandin E2 (PGE2) when contacted with the multimeric ligand, whereby the antigen-presenting cell is activated.
A method for inducing a cytotoxic T lymphocyte (CTL) immune response against an antigen, which comprises:
- contacting an antigen-presenting cell sensitized with an antigen with:
- a. a multimeric ligand that binds to a chimeric protein in the cell, wherein the chimeric protein comprises a membrane targeting region, a ligand-binding region and a CD40 cytoplasmic polypeptide region lacking the CD40 extracellular domain, and
- b. a Pattern Recognition receptor (PRR) ligand;
- whereby a CTL immune response is induced against the antigen.
A method for inducing an immune response against an antigen, which comprises:
- contacting an antigen-presenting cell sensitized with an antigen with a multimeric ligand that binds to a chimeric protein in the cell, wherein:
- a. the chimeric protein comprises a membrane targeting region, a ligand-binding region and a CD40 cytoplasmic polypeptide region lacking the CD40 extracellular domain, and
- b. the antigen-presenting cell is not contacted with prostaglandin E2 (PGE2) when contacted with the multimeric ligand;
- whereby an immune response against the antigen is induced.
A method for inducing a cytotoxic T lymphocyte (CTL) immune response against an antigen, which comprises:
- contacting a human antigen-presenting cell sensitized with an antigen with:
- a. a multimeric molecule having two or more regions that bind to and multimerize native CD40, and
- b. a Pattern Recognition Receptor (PRR ligand);
- whereby a CTL immune response is induced against the antigen.
A method for assessing migration of an antigen-presenting cell to a lymph node, which comprises:
- a. injecting into a subject an antigen-presenting cell that produces a detectable protein, and
- b. determining the amount of the detectable protein in the lymph node of the animal, whereby migration of the antigen-presenting cell to the lymph node is assessed from the amount of the detectable protein in the lymph node.
A method for activating an antigen-presenting cell, which comprises:
- a. transducing an antigen-presenting cell with a nucleic acid having a nucleotide sequence that encodes a chimeric protein, wherein the chimeric protein comprises (i) a membrane targeting region, (ii) a ligand-binding region and (iii-a) a signaling region and/or cytoplasmic region of a pattern recognition receptor (PRR) or (iii-b) an adapter of a PRR;
- and
- b. contacting the antigen-presenting cell with a non-protein multimeric ligand that binds to the ligand-binding region;
- whereby the antigen-presenting cell is activated.
Dependencies are inferred from the claim text.