HLA class II deficient cells, HLA class I deficient cells capable of expressing HLA class II proteins, and uses thereof
AssigneeUniversity of Washington through its Center for Commercialization
InventorsDavid W. Russell, Roli K. Hirata
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Abstract
The invention provides isolated primate cells preferably human cells that comprise a genetically engineered disruption in a human leukocyte antigen (HLA) class II-related gene, which results in deficiency in MHC class II expression and function. This invention also provides isolated cells further comprising a genetically engineered disruption in a beta-2 microglobulin (B2M) gene, which results in HLA class I/class II deficiency. Also provided are the method of using the cells for transplantation and treating a disease condition.
Claims14
An isolated cell comprising a genetically engineered disruption in all copies of a human leukocyte antigen (HLA) class II-related gene, wherein the cell is a human cell, wherein:
- a) the HLA class II-related gene is selected from the group consisting of regulatory factor X-associated ankyrin-containing protein, regulatory factor 5, regulatory factor X associated protein, class II transactivator;
- and
- b) the cell further comprises one or more polynucleotides, wherein the one or more polynucleotides is capable of encoding a single chain fusion HLA class I protein, wherein the single chain fusion HLA class I protein comprises at least a portion of B2M (SEQ ID NO:2) covalently linked to at least a portion of a non-classical HLA class I α chain;
- and
- c) the cell further comprises a genetically engineered disruption in the endogenous β2-microglobulin (B2M) gene (SEQ ID NO:
- 1);
- and
- d) wherein the single chain fusion HLA class I protein is capable of engaging inhibitory receptors on the surface of NK cells.
Dependencies are inferred from the claim text.