ADOPTIVE TRANSFER OF CD8 + T CELL CLONES DERIVED FROM CENTRAL MEMORY CELLS

• US 20080131415A1
• Filed: 10/11/2007
• Published: 06/05/2008
• Est. Priority Date: 11/30/2006
• Status: Abandoned Application

• Current Assignee: City of Hope, Fred Hutchinson Cancer Research Center (Fred Hutchinson Cancer Research Center|Argus Genetics|Mars)
• Original Assignee: Fred Hutchinson Cancer Research Center (Fred Hutchinson Cancer Research Center|Argus Genetics|Mars)
• Inventors: Berger, Carolina, Riddell, Stanley R., Jensen, Michael C.
• Application Number:
  US11/870,776
• Publication Number:
  US 20080131415A1
• Time in Patent Office: Days
• US Class Current: 424/93.71
• CPC Class Codes: A61K 2039/5158 Antigen-pulsed cells, e.g. T-cells
• CPC Class Codes: A61K 2239/31 characterized by the route of administration
• CPC Class Codes: A61K 2239/38 characterised by the dose, timing or administration schedule
• 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 39/0011 Cancer antigens
• 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 39/464412 CD19 or B4
• CPC Class Codes: A61K 39/464424 CD20
• CPC Class Codes: A61K 39/464838 Viral antigens
• CPC Class Codes: C12N 15/85 for animal cells
• CPC Class Codes: C12N 2501/2315 Interleukin-15 (IL-15)
• CPC Class Codes: C12N 5/0636 T lymphocytes
• CPC Class Codes: C12N 5/0638 Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]

Abstract

The present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

Claims

1. In a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering said subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount, the improvement comprising:

administering as said CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, said CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes.

2. The method of claim 1, wherein said CTL preparation is produced by the process of:

(a) collecting a first CTL population from a donor;

(b) separating a CTL subpopulation enriched for CD62L⁺ central memory T lymphocytes and depleted of CD62L⁻

effector memory T lymphocytes to produce a central memory-enriched CTL subpopulation;

(c) expanding said central memory-enriched CTL subpopulation in vitro in a culture medium; and

then

(d) collecting cells from said culture medium to produce said CTL preparation.

3. The method of claim 2, wherein said separating step is carried out by:

(i) contacting said first CTL population to anti-CD62L antibody, wherein said antibody is immobilized on a solid support, so that central memory cells bind to said support;

then (ii) separating said support from said CTL population with central memory cells bound thereto;

(iii) and then separating said central memory cells from said solid support to produce said central memory enriched CTL subpopulation.

4. The method of claim 1, further comprising the step of concurrently administering Interleukin-15 to said subject in an amount effective to increase the proliferation of said central memory T cells in said subject.

5. The method of claim 1, wherein said subject is a human subject.

6. The method of claim 1, wherein said subject is afflicted with cancer.

7. The method of claim 1, wherein said subject is afflicted with an infectious disease.

8. The method of claim 1, wherein said subject is immunodeficient.

9. The method of claim 1, wherein said central memory-enriched T cells are modified in vitro with at least one gene that targets cancer cells.

10. A pharmaceutical formulation consisting essentially of an in vitro expanded primate cytotoxic T lymphocyte (CTL) population, said CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes.

11. The formulation of claim 10, wherein said CTL population is produced by the process of:

(a) collecting a first CTL population from a donor;

(b) separating a CTL subpopulation enriched for CD62L⁺ central memory T lymphocytes and depleted of CD62L⁻

effector memory T lymphocytes to produce a central memory-enriched CTL subpopulation;

(c) expanding said central memory-enriched CTL subpopulation in vitro in a culture medium; and

then

(d) collecting cells from said culture medium to produce said CTL preparation.

12. The formulation of claim 11, wherein said separating step is carried out by:

(i) contacting said first CTL population to anti-CD62L antibody, wherein said antibody is immobilized on a solid support, so that central memory cells bind to said support;

then (ii) separating said support from said CTL population with central memory cells bound thereto;

(iii) and then separating said central memory cells from said solid support to produce said central memory enriched CTL subpopulation.

13. The formulation of claim 10, wherein said central memory-enriched T cells are modified in vitro with at least one gene that targets cancer cells.

14. A method of making a cytotoxic T lymphocyte (CTL) preparation useful for adoptive immunotherapy;

said method comprising the steps of;

(a) collecting a first CTL population from a donor;

(b) separating a CTL subpopulation enriched for CD62L⁺ central memory T lymphocytes and depleted of CD62L⁻

effector memory T lymphocytes to produce a central memory-enriched CTL subpopulation;

(c) expanding said central memory enriched CTL subpopulation in vitro in a culture medium; and

then

(d) collecting cells from said culture medium to produce said CTL preparation.

15. The method of claim 14, wherein said expanding step comprises administering Interleukin-15 to said central memory subpopulation in vitro.

16. The method of claim 14, wherein said central memory-enriched T cells are modified in vitro with at least one gene that targets cancer cells.

17. An in vitro expanded primate cytotoxic T lymphocyte (CTL) preparation produced by the process of claim 14.