Combination of compositions for elimination and enhanced engraftment of hematopoietic stem cells in the bone marrow of a subject
The present invention provides a combination of compositions comprising i) a composition comprising I) a population of T cells, NK cells or cytotoxic immune effector cells comprising a chimeric antigen receptor specific for a stem cell antigen and/or, II) α) a population of T cells, NK cells or cytotoxic immune effector cells comprising a chimeric antigen receptor specific for a tag of a tagged polypeptide, wherein said tagged polypeptide binds specifically to a stem cell antigen, and β) said tagged polypeptide, and ii) a composition comprising a) a population of CD34+ hematopoietic stem cells, and b) one or more accessory or contributory cell populations selected from the group consisting of myeloid cell lineages expressing CD14, CD11b, CD11c, CD123, CD33; CD36; CD47, CD66b, CD235a, CD146 and CD326. A method applying these compositions to a subject in need thereof are also provided.
1 . A method for eliminating hematopoietic stem cells in the bone marrow of a subject suffering from a hematologic malignancy or hemoglobinopathy and increasing engraftment efficiency of a population of CD34+ hematopoietic stem cells, the method comprising administering to said subject
i) a composition comprising:
(I) a population of T cells or NK cells comprising a chimeric antigen receptor specific for a tag of a tagged polypeptide, wherein said tagged polypeptide binds specifically to a hematopoietic stem cell antigen, and
(II) said tagged polypeptide,
thereby specifically eliminating said hematopoietic stem cells in the bone marrow of the subject and leaving unaffected the bone marrow's stromal cells, and
ii) a composition comprising:
a) a population of CD34+ hematopoietic stem cells, and
b) an accessory cell population, wherein the accessory cell population is comprised of myeloid lineage cells that express at least one marker from the group consisting of CD14, CD11b, CD11c, CD123, CD33, CD36, CD47, CD66b, CD235a, CD146 and CD326,
thereby increasing engraftment efficiency into the bone marrow of the subject.
2 . The method according to claim 1 , wherein said population of CD34+ hematopoietic stem cells are genetically engineered cells or healthy cells.
3 . The method according to claim 1 , wherein said accessory cell population comprises at least a population of CD14+ hematopoietic cells.
4 . The method according to claim 1 , wherein said hematopoietic stem cell antigen is c-Kit, CD34, CD33, CD71, CD90, CD131, CD133, or CD135.
5 . The method according to claim 1 , wherein the hemoglobinopathy is thalassemia or sickle cell disease.