Bystander immune suppression as a predictor for response to a vaccine
The present invention relates to antigen-specific immune regulatory response. Methods for detecting an antigen-specific immune regulatory response, methods for selecting candidate vaccine recipients, and methods for improved vaccination strategies are presented.
1. A kit comprising:
a first pharmaceutical composition that comprises a prostate cancer vaccine comprising a nucleic acid;
a second pharmaceutical composition that comprises an agent that suppresses an immunosuppressive function of at least one immune regulatory cell-associated molecule, wherein the agent is an antibody that specifically blocks IL35, IL12p35, or Ebi3, and wherein the at least one immune regulatory cell-associated molecule is selected from the group consisting of IL-35, IL-12p35, and Ebi3;
instructions for administering the first and second pharmaceutical compositions to a subject identified as having an antigen-specific suppressive immune response to the prostate cancer vaccine; and
instructions for determining whether the subject has an antigen-specific suppressive immune response to the prostate cancer vaccine.
2. The kit of claim 1 , wherein the nucleic acid comprises a nucleotide sequence that encodes a prostatic acid phosphatase (PAP) antigen.
3. The kit of claim 1 , wherein the instructions for administering further specify administration of the first and second pharmaceutical compositions to the subject at the same time or sequentially.
4. The kit of claim 1 , wherein the instructions for determining describe the steps of:
(i) administering to an immunocompromised animal peripheral blood mononuclear cells from the subject, wherein the immunocompromised animal is capable of mounting a delayed-type hypersensitivity response;
(ii) administering to the immunocompromised animal a target antigen; and
(iii) determining an antigen-specific immune regulatory response by measuring a delayed-type hypersensitivity response in the immunocompromised animal to the target antigen in an assay configured to distinguish between absence of an effector response to the target antigen and presence of an antigen-specific immune regulatory response, and wherein the subject is selected to receive the vaccine if the cells mediate a delayed-type hypersensitivity response otherwise suppressed by the antigen-specific immune regulatory response.
5. The kit of claim 1 , wherein the instructions for determining instruct characterizing the antigen-specific suppressive immune response as the presence of CD8 + /IL-35 + /CTLA-4 + T-lymphocytes in the subject.
6. A kit comprising:
a first pharmaceutical composition that comprises a prostate cancer vaccine comprising a nucleic acid;
a second pharmaceutical composition that comprises an agent that suppresses an immunosuppressive function of at least one immune regulatory cell-associated molecule, wherein the agent is an antibody that specifically blocks CTLA4, and wherein the at least one immune regulatory cell-associated molecule is CTLA4;
instructions for administering the first and second pharmaceutical compositions to a subject identified as having an antigen-specific suppressive immune response to the prostate cancer vaccine; and
instructions for determining whether the subject has an antigen-specific suppressive immune response to the prostate cancer vaccine.
7. The kit of claim 6 , wherein the nucleic acid comprises a nucleotide sequence that encodes a prostatic acid phosphatase (PAP) antigen.
8. The kit of claim 6 , wherein the instructions for administering further specify administration of the first and second pharmaceutical compositions to the subject at the same time or sequentially.
9. The kit of claim 6 , wherein the instructions for determining describe the steps of:
(i) administering to an immunocompromised animal peripheral blood mononuclear cells from the subject, wherein the immunocompromised animal is capable of mounting a delayed-type hypersensitivity response;
(ii) administering to the immunocompromised animal a target antigen; and
(iii) determining an antigen-specific immune regulatory response by measuring a delayed-type hypersensitivity response in the immunocompromised animal to the target antigen in an assay configured to distinguish between absence of an effector response to the target antigen and presence of an antigen-specific immune regulatory response, and wherein the subject is selected to receive the vaccine if the cells mediate a delayed-type hypersensitivity response otherwise suppressed by the antigen-specific immune regulatory response.
10. The kit of claim 6 , wherein the instructions for determining instruct characterizing the antigen-specific suppressive immune response as the presence of CD8 + /IL-35 + /CTLA-4+T-lymphocytes in the subject.