METHODS FOR OFF-THE- SHELF TUMOR IMMUNOTHERAPY USING ALLOGENEIC T-CELL PRECURSORS

• US 20110052554A1
• Filed: 01/30/2009
• Published: 03/03/2011
• Est. Priority Date: 01/30/2008
• Status: Active Grant

• Current Assignee: Memorial Sloan-Kettering Cancer Center
• Original Assignee: Memorial Sloan-Kettering Cancer Center
• Inventors: Sadelain, Michael, Zakrzewski, Johannes L., Van Der Brink, Marcel R.m.
• Granted Patent: US 10,059,923 B2
• Time in Patent Office: Days
• US Class Current: 424/93.71
• CPC Class Codes: A61K 2039/5156 expressing foreign proteins
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2239/26 Universal/off- the- shelf cellular immunotherapy; Allogenic cells or means to avoid rejection
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61K 39/461 characterised by the cell type used
• CPC Class Codes: A61K 39/4611 T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
• CPC Class Codes: A61K 39/4621 immunosuppressive or immunotolerising
• CPC Class Codes: A61K 39/4631 Chimeric Antigen Receptors [CAR]
• CPC Class Codes: A61K 39/46434 Antigens related to induction of tolerance to non-self
• CPC Class Codes: A61K 39/464412 CD19 or B4
• CPC Class Codes: A61K 39/464495 Prostate specific membrane antigen [PSMA]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: C07K 14/705 : Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/7051 : T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 2319/03 : containing a transmembrane segment
• CPC Class Codes: C12N 2501/23 : Interleukins [IL]
• CPC Class Codes: C12N 2501/26 : Flt-3 ligand (CD135L, flk-2 ligand)
• CPC Class Codes: C12N 2501/42 : Notch; Delta; Jagged; Serrate
• CPC Class Codes: C12N 2502/1394 : Bone marrow stromal cells; whole marrow
• CPC Class Codes: C12N 5/0636 : T lymphocytes

Abstract

The inventive subject matter relates to methods for treating a T-cell deficiency in a subject in need thereof, comprising administering to said subject a T-cell precursor isolated from an allogeneic donor, provided that said allogeneic donor is not MHC-matched to said subject. The inventive methods can be further enhanced by genetic engineering for targeted immunotherapy.

Claims

1. A method for treating a T-cell deficiency in a subject in need thereof, comprising administering to said subject a T-cell precursor isolated from an allogeneic donor, wherein the MHC of said allogeneic donor is not matched to the MHC of said subject.

2. The method of claim 1, wherein said T-cell precursor cell is selected from the group consisting of one or more CD4⁻

CD8⁻

double negative precursor cell lineages, or a combination thereof.

3. The method of claim 2, wherein said double negative precursor cell is selected from the group consisting of DN2(CD44⁺CD25⁺), DN3 (CD44⁻

CD25⁺), DN2/3, an equivalent human DN T cell precursor phenotype, or a combination thereof.

4. The method of claim 2, wherein said double negative precursor cell is derived from lineage lin⁻

Sca-1⁺c-kit^hi or a human equivalent CD34+ lineage.

5. The method of claim 1, provided that said method does not comprise co-administration of allogeneic hematopoietic stem cells.

6. The method of claim 1, provided that said method does not comprise co-administration of immunosuppressive compositions.

7. The method of claim 1, provided that said method does not comprise co-administration of either hematopoietic stem cells or immunosuppressive compositions.

8. The method of claim 1, wherein said non-MHC-matched T-cell precursor additionally comprises a nucleic acid sequence which codes for a chimeric antigen receptor which is capable of expression in said T-cell precursor.

9. The method of claim 1, wherein said non-MHC-matched T-cell precursor expresses a chimeric antigen receptor which is specific for an antigen of a target cancer cell.

10. The method of claim 9, wherein said chimeric antigen receptor expresses an anti-CD19 protein.

11. The method of claim 9, wherein said chimeric antigen receptor is 19z1.

12. The method of claim 9, wherein said non-MHC-matched T-cell precursor cell expresses one or more proteins selected from the group consisting of costimulatory molecules CD26, CD28, CD40, CD80, CD86, CD134, CD154, and combinations thereof.

13. The method of claim 1, wherein said T-cell deficiency is selected from the group consisting of acute lymphoblastic leukemia, acute lymphocytic leukemia, acute myelogenous leukemia, aplastic anemia, chronic myelogenous leukemia, desmoplastic small round cell tumor, Ewing'"'"'s sarcoma, Hodgkin'"'"'s disease, multiple myeloma, myelodysplasia, Non-Hodgkin'"'"'s lymphoma, paroxysmal nocturnal hemoglobinuria, radiation poisoning, chronic lymphocytic leukemia, AL amyloidosis, essential thrombocytosis, polycythemia vera, severe aplastic anemia, neuroblastoma, breast tumors, ovarian tumors, renal cell carcinoma, autoimmune disorders, such as systemic sclerosis, osteopetrosis, inherited metabolic disorders, juvenile chronic arthritis, adrenoleukodystrophy, amegakaryocytic thrombocytopenia, sickle cell disease, severe congenital immunodeficiency, Griscelli syndrome type II, Hurler syndrome, Kostmann syndrome, Krabbe disease, metachromatic leukodystrophy, thalassemia, hemophagocytic lymphohistiocytosis, and Wiskott-Aldrich syndrome.

14. A method for treating a T-cell deficiency in a subject in need thereof, consisting essentially of administering to said subject a T-cell precursor cell isolated from an allogeneic donor, wherein the MHC of said allogeneic donor is not matched to the MHC of said subject.