Activation of marrow infiltrating lymphocytes in hypoxic alternating with normoxic conditions

Abstract

In some aspects, the invention relates to compositions comprising marrow infiltrating lymphocytes (“MILs”). The MILs may be activated MILs. In some aspects, the invention relates to methods for activating MILs, comprising incubating MILs in an environment comprising less than 21% oxygen. In some aspects, the invention relates to methods for treating cancer in a subject, comprising administering to the subject a composition comprising activated MILs.

1 .- 21 . (canceled) 
     
     
         22 . A method for preparing a population of marrow infiltrating lymphocytes (MILs), comprising:
 a) growing MILs in vitro under a hypoxic condition for a first period of time; and   b) growing the MILs under a normoxic condition for a second period of time following said growing in step a).   
     
     
         23 . The method of  claim 22 , wherein the hypoxic condition is less than 21% oxygen. 
     
     
         24 . The method of  claim 23 , wherein the hypoxic condition is about 1% oxygen to about 7% oxygen. 
     
     
         25 . The method of  claim 24 , wherein the hypoxic condition is about 1% to about 3% oxygen. 
     
     
         26 . The method of  claim 25 , wherein the hypoxic condition is about 2% oxygen. 
     
     
         27 . The method of  claim 22 , wherein said first period of time is about 1 day to about 20 days. 
     
     
         28 . The method of  claim 27 , wherein said first period of time is about 3 days to about 14 days. 
     
     
         29 . The method of  claim 28 , wherein said first period of time is about 3 days. 
     
     
         30 . The method of  claim 22 , wherein the normoxic condition is about 21% oxygen. 
     
     
         31 . The method of  claim 22 , wherein said second period of time is about 3 to about 7 days. 
     
     
         32 . The method of  claim 31 , wherein said second period of time is about 4 days. 
     
     
         33 . The method of  claim 22 , wherein the first period of time and second period of time is about 3 days to about 24 days. 
     
     
         34 . The method of  claim 33 , wherein the first period of time and second period of time is about 3 to about 10 days. 
     
     
         35 - 38 . (canceled)