Modulation of antigen immunogenicity by addition of epitopes recognized by NKT cells
Inventors
Assignees
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Publication Number
US-11236127-B2
Publication Date
2022-02-01
Expiration Date
Abstract
The invention describes a method and compounds for the prevention and treatment of infections with intracellular organisms, the treatment of tumors, and the prevention of infectious and allergic diseases by vaccination.
Core Innovation
The invention relates to modifying an immunogenic peptide or polypeptide by introducing or adding a CD1d-binding motif so that the peptide or polypeptide is presented by CD1d and activates NKT cells. In particular, the invention describes identifying a peptide or polypeptide from an agent causing infection, a tumor, or an allergen that does not activate NKT cells when incubated with a cell line expressing CD1d and NKT cells, and then modifying it by introducing at least one CD1d binding motif comprising [FWHY]-X2X3-[ILMV]-X5X6-[FWHY].
The invention further describes selecting a modified peptide or polypeptide that activates NKT cells when the modified peptide or polypeptide is incubated with a cell line expressing CD1d and NKT cells. For peptides or polypeptides having capacity to bind to CD1d, the selection includes determining the ability to activate NKT cells by incubation with cells expressing CD1d, followed by addition of a population of NKT cells, and detecting NKT cell activation.
According to the disclosed embodiments, the modified peptide or polypeptide is capable of activating Type I NKT cells, including CD4+ NKT cells, and inducing cytolytic activity and cytokine production. The invention addresses treating infections with intracellular pathogens and treating tumors by using antigen-derived peptides or polypeptides engineered to activate NKT cells through CD1d-binding motifs, and includes vaccination-related uses such as improving vaccination against infectious agents and allergens by increasing NKT cytokines and downstream immune responses, including B cell and CD4+ T cell responses.
Claims Coverage
The document includes three independent claims. Each claim centers on the same core inventive concept: identify a peptide or polypeptide that does not activate NKT cells via CD1d, introduce at least one CD1d binding motif of the form [FWHY]-X2X3-[ILMV]-X5X6-[FWHY] to generate a modified peptide or polypeptide, select a variant that activates NKT cells, and administer the modified peptide or polypeptide.
CD1d motif engineered modified peptide for NKT-cell activating treatment of infection
Identify a peptide or polypeptide from an agent causing an infection in a mammalian subject that does not activate NKT cells when incubated with a cell line expressing CD1d and NKT cells; introduce at least one CD1d binding motif comprising [FWHY]-X2X3-[ILMV]-X5X6-[FWHY] into the said peptide or polypeptide to generate a modified peptide or polypeptide; select a modified peptide or polypeptide that activates NKT cells; and administer the modified peptide or polypeptide that activates NKT cells to the mammalian subject.
Type I NKT-cell activating CD1d motif engineered peptide administration
Identify a peptide or polypeptide that does not activate NKT cells when incubated with a cell line expressing CD1d and NKT cells; introduce at least one CD1d binding motif comprising [FWHY]-X2X3-[ILMV]-X5X6-[FWHY] into the peptide or polypeptide to generate a modified peptide or polypeptide; select a modified peptide or polypeptide that activates NKT cells; and administer the modified peptide or polypeptide that activates NKT cells to the mammal, wherein the NKT cells are Type I NKT cells.
Tumor treatment using CD1d motif engineered NKT activating peptides with CD4+ cytolytic and cytokine functions
Identify a peptide or polypeptide from the tumor in the mammalian subject wherein the peptide or polypeptide does not activate NKT cells when incubated with a cell line expressing CD1d and NKT cells; introduce at least one CD1d binding motif comprising [FWHY]-X2X3-[ILMV]-X5X6-[FWHY] into the said peptide or polypeptide to generate a modified peptide or polypeptide; select a modified peptide or polypeptide that activates NKT cells and that activates cytolytic activity and cytokine production by CD4+ NKT cells; and administer the modified peptide or polypeptide to the mammalian subject in need of treatment.
Across the independent claims, the inventive coverage is directed to CD1d-motif engineered modified peptides or polypeptides that are selected based on CD1d-binding capacity and NKT activation readouts after incubation with CD1d-expressing cells and addition of a population of NKT cells. The claims cover treatment of infections and tumors, and a method for activating Type I NKT cells in a mammal, with dependent claims focusing on CD4+ cytolytic activity and cytokine production.
Stated Advantages
Activates NKT cells by CD1d presentation, enabling cytolytic activity and cytokine production by CD4+ NKT cells when administered.
Documented Applications
Treating an infection in a mammalian subject by administering a CD1d binding motif engineered modified peptide or polypeptide that activates NKT cells.
Activating Type I NKT cells in a mammal by administering a CD1d binding motif engineered modified peptide or polypeptide that activates NKT cells.
Treating a tumor in a mammalian subject by administering a tumor-derived CD1d motif engineered modified peptide or polypeptide that activates NKT cells and activates cytolytic activity and cytokine production by CD4+ NKT cells.
Improving vaccination against infectious agents and allergens by increasing NKT cytokines and downstream immune responses, including B cell and CD4+ T cell responses.
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