| US 7,479,269 B2 | ||
| Methods for selectively enriching TH1 and TH2 cells | ||
| Carl H. June, Merion Station, Pa. (US); Craig B. Thompson, Merion, Pa. (US); Gary J. Nabel, Washington, D.C. (US); Gary S. Gray, Brookline, Mass. (US); and Paul D. Rennert, Holliston, Mass. (US) | ||
| Assigned to Genetics Institute, LLC, Cambridge, Mass. (US); Regents of the University of Michigan, Ann Arbor, Mich. (US); and The United States of America as represented by the Secretary of the Navy, Washington, D.C. (US) | ||
| Filed on Jan. 05, 2006, as Appl. No. 11/326,148. | ||
| Application 11/326148 is a continuation of application No. 11/029188, filed on Jan. 04, 2005, granted, now 7,232,566. | ||
| Application 11/029188 is a continuation of application No. 08/592711, filed on Jan. 26, 1996, granted, now 6,905,680. | ||
| Application 08/592711 is a continuation in part of application No. 08/435816, filed on May 04, 1995, granted, now 6,534,055. | ||
| Application 08/435816 is a continuation in part of application No. 08/403253, filed on Mar. 10, 1995, granted, now 6,352,694. | ||
| Application 08/403253 is a continuation in part of application No. 08/253964, filed on Jun. 03, 1994, abandoned. | ||
| Prior Publication US 2006/0099177 A1, May 11, 2006 | ||
| This patent is subject to a terminal disclaimer. | ||
| Int. Cl. A61K 35/14 (2006.01); A61K 35/26 (2006.01); A61K 35/28 (2006.01) | ||
| U.S. Cl. 424—93.71 [424/93.1; 424/93.7; 424/534; 424/577; 424/578; 435/2; 435/375; 435/377] | 12 Claims |
| 1. A method for selectively expanding a population of TH1 cells from a population of CD4+ T cells in vitro to sufficient numbers for use in therapy, comprising:
a) contacting a population of CD4+ T cells with:
(1) an agent which provides a primary activation signal to the CD4+ T cells thereby activating the CD4+ T cells, wherein the agent is selected from the group consisting of an anti-CD3 antibody or a CD3-binding fragment thereof,
an anti-CD2 antibody or a CD2-binding fragment thereof, and an antigen in a form suitable to trigger a primary activation
signal in the CD4+T cell when complexed with the TCR/CD3 complex; and
(2) an anti-CD28 antibody or a CD28-binding fragment thereof, thereby stimulating the activated CD4+ T cells, such that the CD4+ T cells are stimulated to proliferate and produce at least one TH1 cytokine selected from the group consisting of IL-2 and
IFN-γ,
the agent which provides a primary activation signal and the anti-CD28 antibody or CD28-binding fragment thereof being attached
to the same surface,
wherein an increase in the amount of the at least one TH1 cytokine following activation and stimulation of the CD4+ T cells compared to the amount of the at least one TH1 cytokine produced by CD4+ T cells that have not been activated as in (1) and stimulated in (2), indicates selective expansion of the TH1 cells.
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