Generation of human regulatory T cells by bacterial toxins for the treatment of inflammatory disorders
AssigneeUniversity of Southern California
InventorHomayoun H. Zadeh
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Abstract
An adoptive immunotherapy using ex vivo-generated regulatory T cells may be used for the suppression of undesireable immune response. T cells are to be obtained from the patient's blood, and upon exposure to a set of toxins from the pathogen A. actinomycetemcomitans, the population of regulatory T cells will be enriched ex vivo and adoptively transferred back to the patient. The novel aspect of the present invention is that it generates large numbers of type 1 regulatory T cells, which secrete Interleukin-10.
Claims19
A method of generating regulatory cells comprising:
- incubating one or more proteins comprising a cytolethal distending toxin (cdt), a leukotoxin (ltx) and/or a heat shock protein with blood cells for a time sufficient to induce differentiation, selective enrichment, and/or promoting proliferation of regulatory T cells, wherein said proteins are secreted from at least one pathogenic organism, wherein said pathogenic organism that secretes leukotoxin is Actinobacillus actinomycetemcomitans, Mannheimia (Pasteurella) haemolytica, or Fusobacterium necrophorum.
A method of generating regulatory cells comprising:
- incubating one or more proteins comprising a cytolethal distending toxin (cdt), a leukotoxin (ltx) and/or a heat shock protein with blood cells for a time sufficient to induce differentiation, selective enrichment, and/or promoting proliferation of regulatory T cells, wherein said proteins are secreted from at least one pathogenic organism, wherein said pathogenic organism that secretes a cytolethal distending toxin is Actinobacillus actinomycetemcomitans, Escherichia coli Shigella dysentarie, Haemophilus ducreyi, Campylobacter upsaliensis, Campylobacter jejuni Helicobacter hepaticus, and Salmonella. enterica serovar Typhi genome.
A method of generating regulatory cells comprising:
- incubating one or more proteins comprising a cytolethal distending toxin (cdt), a leukotoxin (ltx) and/or a heat shock protein with blood cells for a time sufficient to induce differentiation, selective enrichment, and/or promoting proliferation of regulatory T cells, wherein said proteins are expressed from at least one expression plasmid.
A method of generating regulatory cells comprising:
- incubating one or more proteins comprising a cytolethal distending toxin (cdt), a leukotoxin (ltx) and/or a heat shock protein with blood cells for a time sufficient to induce differentiation, selective enrichment, and/or promoting proliferation of regulatory T cells, wherein said heat shock gene is GroEL.
A method of generating regulatory cells comprising:
- incubating one or more proteins comprising a cytolethal distending toxin (cdt), a leukotoxin (ltx) and/or a heat shock protein with blood cells for a time sufficient to induce differentiation, selective enrichment, and/or promoting proliferation of regulatory T cells, wherein said blood cells are concentrated peripheral blood mononuclear cells.
A method of generating regulatory cells comprising:
- incubating one or more proteins comprising a cytolethal distending toxin (cdt), a leukotoxin (ltx) and/or a heat shock protein with blood cells for a time sufficient to induce differentiation, selective enrichment, and/or promoting proliferation of regulatory T cells, wherein said regulatory T cells are Tr1.
A method of inducing differentiation and promoting proliferation of regulatory T cells comprising:
- incubating peripheral blood mononuclear cells in the presence of at least three proteins, cytolethal distending toxin (cdt), leukotoxin (ltx) and a heat shock protein;
- and
- selecting for Tr1 cells.
A composition comprising an expression vector comprising a coding sequence for a cytolethal distending toxin (cdt), a leukotoxin (ltx) and a heat shock protein.
Dependencies are inferred from the claim text.