Compositions and methods for inhibition of lineage specific antigens

Abstract

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

What is claimed is: 
     
         1 . An isolated population of cells comprising genetically engineered human hematopoietic cells that are engineered such that they are deficient in a lineage-specific cell-surface antigen which is expressed by their naturally-occurring hematopoietic cell counterpart. 
     
     
         2 . The isolated population of cells of  claim 1 , wherein the lineage-specific cell-surface antigen is an antigen that is naturally associated with human leukocytes, a subpopulation of human leukocytes, human myeloid cells, or human plasma cells. 
     
     
         3 . The isolated population of cells of  claim 1 , wherein the lineage-specific cell-surface antigen is associated with a hematologic malignancy. 
     
     
         4 . The isolated population of cells of  claim 3 , wherein the hematologic malignancy is a myeloid malignancy. 
     
     
         5 . The isolated population of cells of  claim 3 , wherein the hematologic malignancy is a lymphoid malignancy. 
     
     
         6 . The method of  claim 3 , wherein the hematopoietic malignancy is Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, acute myeloid leukemia, chronic myelogenous leukemia, acute lymphoblastic leukemia, chronic lymphoblastic leukemia, and multiple myeloma. 
     
     
         7 . The isolated population of cells of  claim 1 , wherein the lineage-specific cell-surface antigen is a cluster of differentiation (CD) antigen. 
     
     
         8 . The isolated population of cells of  claim 7 , wherein the CD antigen is selected from the group consisting of CD19, CD13, CD20, CD22, CD38, CD123, CD33, CD45, CD70, CD312, CD191, CD85D, CD117, CD96, and CD269. 
     
     
         9 . The isolated population of cells of  claim 8 , wherein the CD antigen is CD33. 
     
     
         10 . The isolated population of cells of  claim 8 , wherein the CD antigen is CD19. 
     
     
         11 . The isolated population of cells of  claim 1 , wherein the population of cells comprises human hematopoietic cells selected from the group consisting of a hematopoietic stem cell, a progenitor cell, a myeloid progenitor cell, a lymphoid progenitor cell, a myeloid cell, a lymphoid cell, or any combination(s) thereof. 
     
     
         12 . The isolated population of cells of  claim 1 , wherein the population of cells comprises genetically engineered hematopoietic stem cells. 
     
     
         13 . The isolated population of cells of  claim 1 , wherein the human hematopoietic cells are obtained from bone marrow, blood, umbilical cord, or peripheral blood mononuclear cells (PBMCs) of a human subject. 
     
     
         14 . The isolated population of cells of  claim 1 , wherein an endogenous gene encoding the lineage-specific cell-surface antigen in the hematopoietic cells is engineered using genome editing. 
     
     
         15 . The isolated population of cells of  claim 14 , wherein the whole or a portion of the endogenous gene encoding the lineage-specific cell-surface antigen is deleted. 
     
     
         16 . The isolated population of cells of  claim 14 , wherein the level of the lineage-specific cell-surface antigen is reduced in the engineered hematopoietic cells as compared with the level of the lineage-specific cell-surface antigen expressed by their naturally-occurring hematopoietic cell counterpart. 
     
     
         17 . The isolated population of cells of  claim 14 , wherein the genome editing is via a CRISPR system. 
     
     
         18 . The isolated population of cells of  claim 17 , wherein the CRISPR system comprises a guide nucleic acid that hybridizes to a coding or non-coding sequence of the endogenous gene encoding the lineage-specific cell-surface antigen. 
     
     
         19 . The isolated population of cells of  claim 17 , wherein the CRISPR system cleaves or produces an insertion, deletion andor substitution of one or more nucleotides in a coding region or a non-coding region of an endogenous gene encoding the lineage-specific cell-surface antigen. 
     
     
         20 . The isolated population of cells of  claim 19 , wherein the lineage-specific cell-surface antigen is CD33. 
     
     
         21 . The isolated population of cells of  claim 19 , wherein the lineage-specific cell-surface antigen is CD19.