US 9,809,797 B2Granted

Enhanced generation of cytotoxic T-lymphocytes by IL-21 mediated FOXP3 suppression

AssigneeNational Institutes of Health (Nih) U.S. Dept. of Health and Human Services (Dhhs) Division of Extramural Inventions and Technology

InventorsCassian Yee, Yongqing Li

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Abstract

A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+ T lymphocytes prior to antigen stimulation; (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+ T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described.

Claims7

Dependent claims

A pharmaceutical formulation comprising a single T cell population type, wherein said T cell population consists of CD8+CD25− antigen-specific human cytotoxic T lymphocyte (CTL) cells specific for an antigen, said formulation being prepared by a process comprising:

(a) sorting a lymphocyte subpopulation depleted of CD25+ cells from a first lymphocyte population of peripheral blood mononuclear cells (PBMC) to produce a CD8+CD25− subpopulation;
(b) promoting the production of antigen-specific CTL cells in said subpopulation by in vitro culturing the sorted CD8+CD25− subpopulation with antigen in a medium containing interleukin-21, wherein the number of antigen specific CD8+ CTL are enriched in said CD8+CD25− subpopulation by at least 100-fold, as compared to that seen in the same lymphocyte population not subjected to either said separating step (a) or this promoting step (b);
and
(c) formulating antigen-specific CTL cells produced therefrom into a pharmaceutical formulation, and
wherein said pharmaceutical formulation comprises at least 109 CTL cells.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application: 12/677,035Filed 25 Sep 2008 · us provisional application
Priority: 3 Oct 2007
Published: US 2010/0330056 A130 Dec 2010
Granted: 7 Nov 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification21 codes

C12N 5/0636
Cells from the blood or the immune system: t lymphocytes
A61K 31/41
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having five-membered rings with two or more ring hetero atoms, at least…
A61K 40/11
Characterised by the cell type used: t-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer…
A61K 40/4243
Transcription factors, e.g. SOX or c-MYC: wilms tumor 1 [WT1]