Cells expressing Th1 characteristics and cytolytic properties
A novel cell type has been generated that has both Th1 characteristics and cytolytic activity. These Th1/killer cells are CD4+ cells purified from peripheral blood and manipulated to have Th1 characteristics such as production of IFN-gamma combined with cytolytic activity similar to cytotoxic T-cells (CTL). The CTL activity is targeted toward diseased cells, not normal cells. The cytolytic activity of the Th1/killer cells is mediated by Granzyme B-Perforin mechanism and results in apoptotic death of diseased cells. Methods of producing and using these Th1/killer cells include isolating CD4+ cells from peripheral blood, activating the CD4+ T-cells to form Th1/killer cells and administering these Th1/killer cells with the cytolytic activity to a patient wherein the Th1/killer cells are allogeneic to the patient.
1 . A composition comprising Th1/killer cells wherein the Th1/killer cells have Th1 characteristics and cytolytic activity.
2 . The composition of claim 1 wherein the cytolytic activity comprises NK characteristics.
3 . The composition of claim 1 wherein the Th1/killer cells express granzyme B and perforin.
4 . The composition of claim 1 wherein the Th1/killer cells express IFN-gamma.
5 . The composition of claim 1 wherein the Th1/killer cells have substantially reduced or no expression of IL-4.
6 . The composition of claim 1 wherein the Th1/killer cells are CD4+ cells.
7 . The composition of claim 1 wherein the Th1/killer cells are formulated with cross-linking agent for CD3 and CD28
8 . The composition of claim 1 wherein the Th1/killer cells are derived from normal donor peripheral blood.
9 . The composition of claim 1 wherein the composition comprises clinically-relevant number of the Th1/killer cells.
10 . The composition of claim 1 wherein the composition comprises at least about 1×10 7 cells.
11 . The composition of claim 1 wherein the composition comprises at least about 1×10 8 cells.
12 . The composition of claim 1 wherein the cytolytic activity of the Th1/killer cells specifically inactivates diseased cells and not normal cells.
13 . The composition of claim 12 wherein the diseased cells comprise cancerous cells, infected cells or combinations thereof.