Immunogenic chimeras comprising nucleic acid sequences encoding endoplasmic reticulum signal sequence peptides and at least one other peptide, and their uses in vaccines and disease treatments
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsNicholas P. Restifo, Steven A. Rosenberg, Jack R. Bennick, Igor Bacik, Jonathan W. Yewdell
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Abstract
Immunogenic chimeric proteins comprising an endoplasmic reticulum signal sequence and at least one other peptide are disclosed. The invention relates to the design of vaccinia virus constructs capable of directing host organism synthesis of immunogenic chimeric proteins which can be used as immunogens, as vaccines, or in methods of treatment for cancer, infectious diseases, or autoimmune diseases.
Claims15
A method for obtaining mammalian T cells which exhibit a response to a tumor peptide, viral peptide, autoimmune disease peptide, bacterial peptide or parasitic peptide, said method comprising:
- (a) administering to a mammal in an amount effective to elicit a T cell response to said tumor peptide, viral peptide, autoimmune disease peptide, bacterial peptide or parasitic peptide a chimeric protein comprising an endoplasmic reticulum signal sequence peptide and at least one other peptide selected from the group consisting of tumor peptides, viral peptides, bacterial peptides, parasitic peptides and autoimmune disease peptides;
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- (b) isolating said T cells from said mammal.
A method for obtaining mammalian T cells which exhibit a response to a tumor peptide, viral peptide, autoimmune disease peptide, bacterial peptide or parasitic peptide, said method comprising:
- immunizing isolated mammalian T cells with target cells, said target cells having been exposed to a chimeric protein comprising an endoplasmic reticulum signal sequence peptide and at least one other peptide selected from the group consisting of tumor peptides, viral peptides, bacterial peptides, parasitic peptides and autoimmune disease peptides in an amount effective to elicit a T cell response to said other peptide.
An isolated T cell having increased peptide-specific reactivity, said T cell having been exposed to a chimeric protein comprising an endoplasmic reticulum signal sequence peptide and at least one other peptide selected from the group consisting of tumor peptides, viral peptides, bacterial peptides, parasitic peptides and autoimmune disease peptides, said T cell having a reactivity to said other peptide at least three times greater than the base line reactivity of T cell exposed to said other peptide in the absence of an endoplasmic reticulum signal sequence peptide where said reactivity is measured in a .sup.51 Cr cytotoxicity release assay at an effector:target ratio of at least 50:1 using target cells pulsed with said other peptide.
Dependencies are inferred from the claim text.