Devices, systems and methods for inhibiting invasion and metasases of cancer
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. A method comprising:
1) providing a) living human tumor cells obtained from a biopsy and b) a microfluidic device comprising a body having a central microchannel therein; and an at least partially porous membrane positioned within the central microchannel, the membrane configured to separate the central microchannel to form a first central microchannel and a second central microchannel, the membrane comprising a top surface and a bottom surface, said top surface comprising living immune cells;
2) introducing said living tumor cells into said microfluidic device under conditions such that at least a portion of said living tumor cells contact with said immune cells; and
3) incubating said living tumor cells in said microfluidic device to produce incubated tumor cells that express one or more tumor markers.
2. The method of claim 1 , further comprising detecting one or more tumor markers 11 days after said introducing of step 2).
3. The method of claim 1 , further comprising determining whether said immune cells cause tumor cell death.
4. The method of claim 1 , further comprising 5) introducing a checkpoint inhibitor in said microfluidic device, and 6) determining whether said checkpoint inhibitor causes tumor cell death.
5. The method of claim 4 , wherein said checkpoint inhibitor is an antibody.
6. The method of claim 5 , wherein said antibody binds the programmed death 1 (PD-1) receptor on said immune cells.
7. The method of claim 5 , wherein said antibody binds the programmed death ligand 1 (PD-L1) ligand on the tumor cells.
8. The method of claim 1 , wherein immune cells are deposited within a gel layer.
9. The method of claim 1 , wherein said immune cells comprise fibroblasts.
10. The method of claim 1 , wherein said tumor cells comprise melanoma cells.
11. The method of claim 10 , wherein said one or more tumor markers comprises microphthalmia-associated transcription factor.