Devices, systems and methods for inhibiting invasion and metastases of cancer

Abstract

The invention generally relates to a microfluidic platforms or “chips” for testing and understanding cancer, and, more specifically, for understanding the factors that contribute to cancer invading tissues and causing metastases. Tumor cells are grown on microfluidic devices with other non-cancerous tissues under conditions that simulate tumor invasion. The interaction with immune cells can be tested to inhibit this activity by linking a cancer chip to a lymph chip.

1 - 44 . (canceled) 
     
     
         45 . A method comprising:
 (a) providing a microfluidic device comprising an at least partially porous membrane, the membrane comprising a first surface and a second surface, the first surface comprising living epithelial cells in contact with and living tumor cells; and   (b) introducing immune cells in the microfluidic device.   
     
     
         46 . The method of  claim 45 , wherein said second surface comprises living endothelial cells. 
     
     
         47 . The method of  claim 45 , further comprising introducing an agent in the microfluidic device, and determining whether the agent causes tumor cell death. 
     
     
         48 . The method of  claim 47 , wherein said agent is a checkpoint inhibitor. 
     
     
         49 . The method of  claim 48 , in which the checkpoint inhibitor is an antibody. 
     
     
         50 . The method of  claim 49 , in which the antibody binds the PD-1 receptor on the immune cells. 
     
     
         51 . The method of  claim 49 , in which the antibody binds the PD-L1 ligand on the tumor cells. 
     
     
         52 . The method of  claim 45 , wherein said immune cells comprise fibroblasts. 
     
     
         53 . The method of  claim 45 , wherein said immune cells comprise lymphocytes. 
     
     
         54 . The method of  claim 45 , wherein said immune cells comprise T cells. 
     
     
         55 . The method of  claim 54 , wherein said T cells are primed T cells. 
     
     
         56 . The method of  claim 54 , wherein said T cells comprise CAR-T cells. 
     
     
         57 . A method comprising:
 a) providing first and second microfluidic devices in fluidic communication, said a) first microfluidic device comprising a membrane comprising a first surface and a second surface, said i) first surface comprises living epithelial cells, and living tumor cells in contact with said epithelial cells, said ii) second surface comprising living endothelial cells; said b) second microfluidic device comprising immune cells; and   b) detecting recruitment of at least a portion of said immune cells such that said tumor cells are contacted by said immune cells.   
     
     
         58 . The method of  claim 57 , wherein said immune cells comprise lymphocytes. 
     
     
         59 . The method of  claim 57 , wherein said immune cells comprise T cells. 
     
     
         60 . The method of  claim 59 , wherein said T cells are primed T cells. 
     
     
         61 . The method of  claim 59 , wherein said T cells comprise CAR-T cells. 
     
     
         62 . A system comprising first and second microfluidic devices in fluidic communication, said a) first microfluidic device comprising a membrane comprising a first surface and a second surface, said i) first surface comprises living epithelial cells, and living tumor cells in contact with said epithelial cells, said ii) second surface comprising living endothelial cells; said b) second microfluidic device comprising immune cells. 
     
     
         63 . The system of  claim 62 , wherein said membrane is coated with at least one attachment molecule that supports adhesion of said living cells. 
     
     
         64 . The system of  claim 62 , wherein said tumor cells are from a biopsy. 
     
     
         65 . The system of  claim 62 , wherein said tumor cells are mammalian tumor cells. 
     
     
         66 . The system of  claim 62 , wherein said tumor cells are human tumor cells. 
     
     
         67 . The system of  claim 62 , wherein said immune cells comprise lymphocytes. 
     
     
         68 . The system of  claim 62 , wherein said immune cells comprise T cells. 
     
     
         69 . The system of  claim 68 , wherein said T cells are primed T cells. 
     
     
         70 . The system of  claim 68 , wherein said T cells comprise CAR-T cells.