End-to-end cell therapy automation

Abstract

The present disclosure provides an automated method of producing genetically modified immune cells, including chimeric antigen receptor T (CAR T) cells, utilizing a fully-enclosed cell engineering system.

1 . An automated cell engineering system comprising:
 a first chamber for storage of a cell culture media at a first temperature;   a second chamber for carrying out activation and expansion of an immune cell culture at a second temperature;   a thermal barrier for insulating the first chamber from the second chamber; and   one or more fluidics pathways fluidly connecting the second chamber to the first chamber,   wherein the one or more fluidics pathways provide recirculation, removal of waste and homogenous gas exchange and distribution of nutrients to the second chamber without contaminating cells within the second chamber.   
     
     
         2 . The system of  claim 1 , wherein the thermal barrier thermally isolates the first chamber from the second chamber, and wherein the first temperature is lower than the second temperature. 
     
     
         3 . The system of  claim 1 , wherein the second chamber is a cell culture chamber. 
     
     
         4 . The system of  claim 3 , wherein the cell culture chamber comprises a non-flexible material. 
     
     
         5 . The system of  claim 1 , further comprising one or more of a temperature sensor, a pH sensor, a glucose sensor, an oxygen sensor, a carbon dioxide sensor, and an optical density sensor. 
     
     
         6 . The system of  claim 5 , further comprising a pump configured to drive fluid to and/or from the second chamber in response to monitoring one or more the temperature sensor, the pH sensor, the glucose sensor, the oxygen sensor, the carbon dioxide sensor, and the optical density sensor. 
     
     
         7 . The system of  claim 1 , further comprising a pump configured to drive fluid through the one or more fluidics pathways without disturbing the cells within the second chamber. 
     
     
         8 . The system of  claim 1 , further comprising a cassette having a plurality of chambers including the first chamber and the second chamber. 
     
     
         9 . The system of  claim 1 , wherein the one or more fluidics pathways comprise a silicone-based tubing component that allows oxygenation through the tubing component. 
     
     
         10 . A cassette for use in an automated cell engineering system, the cassette comprising:
 a first chamber for carrying out activation, transduction and expansion of an immune cell culture; and   a second chamber for storage of a cell culture media;   a thermal barrier for insulating the first chamber from the second chamber; and   wherein the first chamber includes:
 one or more fluidics pathways connecting the first chamber to the second chamber, wherein the one or more fluidics pathways provide recirculation, removal of waste and homogenous gas exchange and distribution of nutrients to the first chamber without contaminating cells within the first chamber. 
   
     
     
         12 . The cassette of  claim 10 , further comprising a plurality of chambers containing one or more of a reagent, media, and/or vectors. 
     
     
         13 . The cassette of  claim 12 , wherein the one or more fluidics pathways fluidly couple each chamber of the plurality of chambers to the first chamber. 
     
     
         14 . The cassette of  claim 10 , further comprising a valve configured to control fluid traveling through the one or more fluidics pathways without contacting the fluid. 
     
     
         15 . The cassette of  claim 10 , further comprising a pump configured to drive fluid through the one or more fluidics pathways without disturbing the cells within the first chamber. 
     
     
         16 . The cassette of  claim 10 , wherein the one or more fluidics pathways comprise a silicone-based tubing component that allows oxygenation through the tubing component. 
     
     
         17 . A method for automated production of a T cell culture within a fully enclosed automated cell engineering system, the method comprising:
 disposing the T cell culture in a first chamber of the fully enclosed automated cell engineering system;   conducting media stored in a second chamber of the fully enclosed automated cell engineering system to the first chamber to feed, wash, and/or oxygenate the T cell culture;   monitoring, via a sensor, one or more parameters of the first chamber, the one or more parameters including one or more of a temperature, a pH level, a glucose level, an oxygen level, a carbon dioxide level, and an optical density level; and   automatically adjusting the one or more parameters based on the monitoring, wherein the automatically adjusting the one or more parameters comprises activating a pump and conducting the media from the second chamber through one or more fluidic pathways to the first chamber based on the monitoring.   
     
     
         18 . The method of  claim 17 , conducting the media to the first chamber does not disturb the T cell culture.