Gammadelta t cell expansion procedure

Abstract

A method for expanding a population of γδ T-cells is provided in which isolated activated Peripheral Blood Mononuclear Cells (PBMCs) are cultured in a medium comprising transforming growth factor beta (TGF-β) under conditions in which the production of effector γδ T-cells having therapeutic activity against malignant disease is favored. The use of TGF-β in the production of effector cells in particular Vγ9Vδ2 T-cells is also described and claimed.

1 . A method for expanding a population of effector γδ T-cells, said method comprising culturing isolated activated Peripheral Blood Mononuclear Cells (PBMCs) in a medium comprising transforming growth factor beta (TGF-β) and Interleukin-2 (IL-2), wherein the medium does not contain fetal calf serum or fetal bovine serum. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method according to  claim 1 , wherein no additional cytokines are present in the medium. 
     
     
         5 . The method according to  claim 1 , wherein the medium is a serum-free medium or contains human AB serum. 
     
     
         6 . The method according to  claim 1 , further comprising a preceding step of adding an activator for Vγ9Vδ2 T-cells . 
     
     
         7 . The method according to  claim 6 , wherein the activator is an aminobisphosphonate. 
     
     
         8 . The method according to  claim 1 , wherein the PBMCs are human PBMCs. 
     
     
         9 . The method according to  claim 8 , wherein the PBMCs are from a healthy human. 
     
     
         10 . The method according to  claim 1 , further comprising a subsequent step of removing CD19 B cells and/ or αβ T-cells from the expanded product. 
     
     
         11 . A method for increasing the yield of effector vδ T-cells expanded in-vitro, said method comprising carrying out the method according to  claim 1 . 
     
     
         12 . A method for enhancing the anti-cancer efficacy of vδ T-cells expanded in-vitro, said method comprising carrying out the method according to  claim 1 . 
     
     
         13 - 14 . (canceled) 
     
     
         15 . T-cells obtained by the method according to  claim 1 . 
     
     
         16 - 21 . (canceled) 
     
     
         22 . The method of  claim 7 , wherein the aminobisphosphonate is zoledronic acid, alendronic acid, pamidronic acid, ibandronic acid, or a salt thereof. 
     
     
         23 . The method of  claim 22 , wherein the aminobisphosphonate is zoledronic acid or a salt thereof.