Process for t cell expansion

Abstract

An in vitro expansion process for rapid expansion of antigen specific T cells, such as allogeneic antigen specific T cells comprising the steps culturing in a gas permeable vessel a population of PBMCs (such as allogeneic PBMCs) in the presence of antigen, for example a peptide or peptide mix relevant to a target antigen(s), in the presence of an exogenous cytokine characterized in that the expansion to provide the desired population of T cells is 14 days or less, for example 9, 10, 11 or 12 days, such as 10 days. The disclosure also extends to T cell populations generated by and obtained from the method and the use of same in therapy.

1 . An in vitro expansion process for rapid expansion of antigen specific T cells, comprising the step of culturing in a gas permeable vessel a population of PBMCs in the presence of an antigen selected from the group consisting of a peptide and a peptide mix relevant to a target antigen(s); wherein the culturing is performed in the presence of an exogenous cytokine wherein the cytokine is other than exogenous IL-2; and wherein media and nutrients are not added or changed after initiation of the expansion process. 
     
     
         2 . An in vitro expansion process according to  claim 1 , wherein the expansion to provide the desired population of T cells is 14 days or less. 
     
     
         3 . An in vitro expansion process according to  claim 1 , wherein the exogenous cytokine is selected from the group comprising IL-4, IL-7, IL-15 or a combination thereof. 
     
     
         4 . An in vitro expansion process according to  claim 2 , wherein the exogenous cytokine is selected from the group comprising IL-4, IL-7, IL-12, IL-15 or a combination thereof. 
     
     
         5 . An in vitro expansion process according to  claim 3 , wherein the exogenous cytokine is a combination of IL-4 and IL-7. 
     
     
         6 . An in vitro process according to  claim 1 , wherein the culture is performed in the presence of a T cell expansion medium. 
     
     
         7 . An in vitro process according to  claim 1 , wherein the peptide mix comprises between 2 and 500 peptides, 2 to 400 peptides, 2 to 300 or 2 to 200 peptides. 
     
     
         8 . An in vitro process according to  claim 7 , wherein the peptides overlap by 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 or more amino acids. 
     
     
         9 . An in vitro process according to  claim 1 , wherein the peptides are on average about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acids in length. 
     
     
         10 . An in vitro process according to  claim 1 , wherein the expansion is performed for 14 days or less. 
     
     
         11 . An in vitro process according to  claim 1 , wherein the expansion is performed for 13, 12, 11, 10 days or less. 
     
     
         12 . An in vitro process according to  claim 1 , wherein the initial PBMC sample derived from a donor is a mobilised sample or mobilised apheresis sample. 
     
     
         13 . An in vitro process according to  claim 1 , wherein the gas permeable vessel is a GRex system or a derivative or an equivalent system. 
     
     
         14 . An in vitro process according to  claim 13 , wherein the GRex system has been adapted to provide a closed system, suitable for aseptic manufacture. 
     
     
         15 . An in vitro process according to  claim 1 , wherein the process is performed aseptically or in a clean room. 
     
     
         16 . An in vitro A process according  claim 1 , which comprises the further step of preparing a pharmaceutically acceptable composition comprising the further step of adding a diluent, stabilizer, preservative and/or other pharmaceutically acceptable excipient. 
     
     
         17 . An in vitro A process according to  claim 16 , which comprises the further step of filling the antigen specific T cell population or a pharmaceutical composition comprising the same into a container such as infusion bag and sealing the container. 
     
     
         18 . An in vitro process for rapid expansion of antigen specific T cells, comprising the step of culturing in a gas permeable vessel a population of PBMCs in the presence of an antigen selected from the group consisting of a peptide and a peptide mix relevant to a target antigen(s); wherein the culturing is performed in the presence of an exogenous cytokine wherein the cytokine is other than exogenous IL-2; and wherein the process consists of expanding the antigen-specific T cells for 14, 13, 12, 11, 10, 9, 8, 7 days or less. 
     
     
         19 - 36 . (canceled) 
     
     
         37 . An in vitro process according to  claim 1 , wherein the target antigen is a CMV-specific antigen.