Description of the Invention
Pear’s technology is based on the combination of microfluidics (body on a chip) and biomaterials (hydrogel mimicking human tumor microenvironment) to recreate the lifecycle of cancer drugs outside a patient’s body.
The body on a chip device is used to mimic a drug’s journey through the human body. It contains a drug injection system, which pumps drugs into a reservoir that circulates blood in circuit. The blood and drugs then arrive at a microfluidic chip contain a chamber with a tumor sample and then a chamber with a liver sample. The setup mimics how drugs are delivered via IV injection into the blood and arrives at the tumor first before being circulated to the liver for metabolism and then being circulated back around to the tumor. This pathway also allows cancer cells to migrate along the hydrogel microenvironment into the blood and downstream to the liver to create metastases. By having blood flow parallel to the hydrogel containing the tumor, we prevent overaccumulation of the drug within the tumor chamber, which would lead to overdosing (false positives).
Cancer is treated with oncology and immuno-oncology.
Human tumor microenvironment
The hydrogel is one of the major components of the human tumor microenvironment. Pear recreates the human tumor microenvironment using a hyaluronic acid backbone and strong physical crosslinking to recreate the mechanical environment of the in vivo extracellular matrix. Hyaluronic acid contains RHAMM receptors, which are critical for cancer cell migration, especially in breast cancer. Supplementary hydrogels are added to further recreate the tumor microenvironment, including collagen for its RGD ligands. Finally, key components of the human tumor microenvironment like proteins, fibroblasts and immune cells are cocultured into the system. The hydrogel is non-immunogenic, so immune cells don’t attack the material, which prevents false positives (the treatment looks like it is working but not because it is attacking the cancer cells).
Preclinical optimization for triple negative breast cancer:
– 45 microfluidic chips
– Tests in triplicates
– 5 individual drugs, 5 2 drug combinations and 5 3 drug combinations
Immunotherapy safety/efficacy testing
– Modified microfluidic chip design
– Coculture of patient tumor+immune sample (Synexa)
– Work with Merck’s store of immunotherapies for proof of concept
– Results analyzed via comparing cytokine concentration to cell viability of healthy and cancer cells