Immunomodulatory cells and uses thereof
AssigneeSinai Health System
InventorsAndras Nagy, Jeffrey Harding, Kristina Nagy
Life of this patent
Estimating the term…
Abstract
Featured are cells and methods of use thereof for modulating an antigen-specific immune response in a subject. The cells comprise a set of transgenes that shield the cells from immune surveillance. The cells can be used to induce immune tolerance to an antigen (e.g., a donor alloantigen or a self-antigen), or to induce an immune response to (e.g., induce the production of antibodies directed against) a non-self antigen.
Claims151
A cell genetically modified to comprise at least one mechanism for inducing immune tolerance to an antigen when administered to a subject, the genetically modified cell comprising a set of transgenes comprising two or more of the following genes:
- PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, or Serpin B9 or Spi6;
- and a transgene encoding a polypeptide comprising an antigen.
A method of inducing immune tolerance in a subject to a donor alloantigen, comprising:
- (i) providing a donor cell expressing a polypeptide comprising the donor alloantigen;
- and
- (ii) expressing in the cell a set of transgenes comprising two or more of the following genes:
- PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, or Serpin B9 or Spi6;
- and
- (iii) administering the cell to the subject to induce immune tolerance to the donor alloantigen.
A method of inducing immune tolerance in a subject to a donor alloantigen, comprising:
- (i) providing a cell;
- and
- (ii) expressing in the cell a set of transgenes comprising two or more of the following genes:
- PD-L1, HLAG or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, or Serpin B9 or Spi6;
- (iii) modifying the cell to express a transgene encoding a polypeptide comprising the donor alloantigen;
- and
- (iv) administering the cell to the subject to induce immune tolerance to the donor alloantigen.
A method of inducing immune tolerance in a subject to an antigen, comprising:
- (i) providing a cell;
- and
- (ii) expressing in the cell a set of transgenes comprising two or more of the following genes:
- PD-L1, HLAG or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, or Serpin B9 or Spi6;
- (iii) expressing in the cell a transgene encoding a polypeptide comprising the antigen;
- and
- (iv) administering the cell to the subject to induce immune tolerance to the antigen.
A method of treating a subject having or at risk of developing an autoimmune disease or condition, comprising administering to the subject a cell modified to express a transgene encoding a polypeptide comprising an antigen associated with the autoimmune disease or condition and a set of transgenes comprising two or more of the following genes:
- PD-L1, HLAG or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, or Serpin B9 or Spi6.
A method of inducing an immune response in a subject to an antigen, comprising:
- (i) administering to the subject a first cell expressing a set of transgenes comprising two or more of the following genes:
- PD-L1, HLAG or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, or Serpin B9 or Spi6;
- and
- (ii) administering to the subject a second cell of the same type as the first cell that is modified to express a transgene encoding a polypeptide comprising the antigen and that does not express the set of transgenes.
The method of any one of 52-127, wherein the two or more transgenes are operably linked to a constitutive promoter.
Use of a combination of a first cell and a second cell for inducing an immune response in a subject to an antigen, the use comprising:
- (i) administering to the subject a first cell expressing a set of transgenes comprising two or more of the following genes:
- PD-L1, HLAG or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, or Serpin B9 or Spi6;
- and
- (ii) administering to the subject a second cell of the same type as the first cell that is modified to express a transgene encoding a polypeptide comprising the antigen and that does not express the set of transgenes.
Use of a first cell in the manufacture of a medicament for inducing an immune response in a subject to an antigen, characterized in that the medicament is for administration in a treatment regimen with a second cell, wherein the first cell expresses a set of transgenes comprising two or more of the following genes:
- PD-L1, HLAG or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, and Serpin B9 or Spi6 or a gene encoding a biologic that acts as an agonist of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASLG or FasL, Ccl21 or Ccl21b, Mfge8, or Serpin B9 or Spi6;
- and wherein the second cell is a cell of the same type as the first cell that does not express the set of transgenes and that is modified to express a transgene encoding a polypeptide comprising the antigen.
Dependencies are inferred from the claim text.