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Adoptive transfer of cd8 + t cell clones derived from central memory cells

a technology of central memory cells and t cells, which is applied in the field of adoptive immunotherapy, can solve the problems of limited efficacy of cultured t cells, especially cloned cd8sup>+/sup> t cells, and achieve the effect of increasing the proliferation of central memory t cells

Inactive Publication Date: 2008-06-05
CITY OF HOPE +1
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0007]A first aspect of the present invention is 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 (e.g., grown in vitro for 1, 2, or 3 days up

Problems solved by technology

However, it is apparent from clinical studies that the efficacy of cultured T cells, particularly cloned CD8+ T cells, is frequently limited by their failure to persist after adoptive transfer16,17.

Method used

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  • Adoptive transfer of cd8 + t cell clones derived from central memory cells
  • Adoptive transfer of cd8 + t cell clones derived from central memory cells
  • Adoptive transfer of cd8 + t cell clones derived from central memory cells

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Embodiment Construction

[0041]“T cells” or “T lymphocytes” as used herein may be from any mammalian, preferably primate, species, including monkeys, dogs, and humans. In some embodiments the T cells are allogenic (from the same species but different donor) as the recipient subject; in some embodiments the T cells are autologous (the donor and the recipient are the same); in some embodiments the T cells are syngeneic (the donor and the recipients are different but are identical twins).

[0042]Cytotoxic T lymphocyte (CTL) as used herein refers to a T lymphocyte that expresses CD8 on the surface thereof (i.e., a CD8+ T cell). In some embodiments such cells are preferably “memory” T cells (TM cells) that are antigen-experienced. “Central memory” T cell (or “TCM”) as used herein refers to a CTL that expresses CD62L on the surface thereof (i.e., CD62L+CD8+ cells).

[0043]“Effector memory” T cell (or “TEM”) as used herein refers to a CTL that does not express CD62L on the surface thereof (i.e., CD62L−CD8+ cells).

[004...

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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.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Patent Application Ser. No. 60 / 867,880, filed Nov. 30, 2007, the disclosure of which is incorporated by reference herein in its entirety.GOVERNMENT FUNDING[0002]This invention was made with Government support under Grant Numbers R01CA114536, R01AI053193, CA18029, U01HL66947, and M01RR00037 from the National Institutes of Health. The US Government has certain rights to this invention.FIELD OF THE INVENTION[0003]The present invention concerns methods and compositions for carrying out adoptive immunotherapy.BACKGROUND OF THE INVENTION[0004]Studies in rodents have demonstrated that adoptive immunotherapy with antigen specific T cells is effective for cancer and infections, and there is evidence this modality has therapeutic activity in humans1-8. For clinical applications, it is necessary to isolate T cells of a desired antigen specificity or to engineer T cells to express receptors that target infected or...

Claims

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Application Information

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IPC IPC(8): A61K35/00C12N5/06C12N5/0783
CPCA61K2039/5158C12N5/0636A61K35/17C12N2501/2315C12N5/0638C12N15/85A61K39/0011A61K39/464412A61K2239/31A61K39/464838A61K2239/38A61K39/464424A61K39/4611
Inventor RIDDELL, STANLEY R.BERGER, CAROLINAJENSEN, MICHAEL C.
Owner CITY OF HOPE
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