Methods for handling biological drugs containing living cells

Abstract

The present invention includes methods for handling live cell compositions in non-nutritive buffer. The cells in the compositions maintain their identity and functional characteristics after being stored in non-nutritive media up to about 72 hours. The storage method enables the cells to be manufactured at a processing facility and shipped to a point of care site. The invention also includes compositions that have been stored in non-nutritive buffer at storage temperatures while maintaining the functional characteristics.

What is claimed is: 
     
         1 . A biologic drug composition comprising living cells formulated in non-nutritive buffer, wherein the living cells, after being stored for greater than about 6 hours in the non-nutritive buffer, maintain their identity and at least one functional characteristic that defined the living cells prior to formulation in the non-nutritive buffer, the living cells useful in immunotherapy after storage in the non-nutritive buffer. 
     
     
         2 . The composition of  claim 1  wherein the living cells are placed in a flexible container or syringe, wherein the flexible container or syringe is packaged in a temperature controlled device. 
     
     
         3 . The composition of  claim 1  wherein the living cells are CD4+ cells. 
     
     
         4 . The composition of  claim 1  wherein the living cells are activated Th1 cells 
     
     
         5 . The composition of  claim 4  wherein the Th1 cells are activated by immobilized monoclonal antibodies specific for T-cell surface molecules. 
     
     
         6 . The composition of  claim 5  wherein the monoclonal antibodies are cross-linked. 
     
     
         7 . The composition of  claim 1  wherein the at least one functional characteristic is expression of CD40L, FasL, perforin and granzyme B, expression of costimulatory molecules, expression of adhesion molecules, secretion of cytokines, chemokines or combinations thereof. 
     
     
         8 . The composition of  claim 7  wherein the cytokine secreted is IFN-γ and the level of secretion of IFN-γ after storage is recovered to at least about 80% compared to the level at the time of formulation. 
     
     
         9 . The composition of  claim 1  wherein the live cells in the non-nutritive buffer are stable for at least about 72 hours. 
     
     
         10 . The composition of  claim 2  wherein the composition is maintained at a storage temperature range between about 0° C. and 10° C. 
     
     
         11 . The composition of  claim 1  wherein the concentration of the cells in the non-nutritive buffer is about 10 7  cells/ml greater. 
     
     
         12 . The composition of  claim 4  wherein the Th1 cells are activated by immobilized anti-CD3 and anti-CD28 monoclonal antibodies. 
     
     
         13 . The composition of  claim 1  further comprising at least about 80% viable cells after storage in the non-nutritive buffer. 
     
     
         14 . The composition of  claim 7  wherein the level of expression of CD40L in the cells after storage is at least about 80% compared to the level at the time of formulation. 
     
     
         15 . The composition of  claim 1  wherein the living cells in the non-nutritive buffer are stable for at least about 24 hours. 
     
     
         16 . The composition of  claim 1  wherein the living cells in the non-nutritive buffer are stable for at least about 48 hours.