Development and Optimization for Injectable Thermosensitive Hydrogel-Based Scaffolds with Delivering Granulocyte-Macrophage Colony-Stimulating Factor (Gm-Csf) in Cancer Immunotherapy

Immunotherapy is a novel medical treatment in the field of cancer and several kinds of formulations have been approved to clinical trials or the market. However, the treatment expense is higher and the technologies are still at an early development stage. Nowadays, it is important to further study the immunotherapy in the treatment of cancer. In this project, the technology of U.S. Patent entitled " Thermosensitive injectable hydrogel for drug delivery" published by applicants will be conducted. The hydrogel will be loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) and applied as carrier in cancer immunotherapy. The principle based on the prepared injectable thermosensitive hydrogel carrier with GM-CSF, loading the antigen expression factor isolated from cancer cell, can stimulate the immune response and achieve the effect of killing the cancer cells after subcutaneous injection. The project is conducted in three years. In the first year, PF127 and different molecular weights of hyaluronic acid will be used to prepare thermosensitive hydrogels with different physico-chemical properties. After further loading GM-CSF, it will be measured by 3D imaging to confirm that the pore size of hydrogel is available for dendritic cell migration and evaluated the release mode and the controlling release ability of GM-CSF. In the second year, the hydrogel prepared in the first year will be executed in vitro migration test in mouse dendritic cells. At the same time, we will establish a method for separating antigen expression factors from colorectal and melanoma cancer cells, respectively. Then, the separated antigen expression factors of cancer cells will be loaded into hydrogel and conduct the in vitro immunogenicity test. In the third year, the most optimized hydrogel will be selected to perform animal experiments of colorectal and melanoma cancer and validate the effect of cancer immunotherapy.