IN-SITU CRYO-IMMUNE ENGINEERING FOR CANCER IMMUNOTHERAPY

Smart overview of the Invention

Cancer immunotherapy aims to utilize the body's immune system to combat tumors. However, its effectiveness is often limited by the immunosuppressive environment of tumors, known as the tumor microenvironment (TME), which is typically "cold" and hinders immune response. This application introduces a novel approach called in-situ cryo-immune engineering (ICIE) that transforms this cold TME into a "hot" environment, enhancing the immune system's ability to recognize and attack cancer cells.

Mechanism of In-Situ Cryo-Immune Engineering

The ICIE strategy employs cold-responsive nanoparticles that specifically target cancer cells. During treatment, these nanoparticles release both anticancer drugs and PD-L1 silencing siRNA when exposed to low temperatures. This process induces immunogenic cell death, promoting the maturation of dendritic cells and activating CD8+ cytotoxic T cells, which are essential for an effective immune response against tumors.

Advantages Over Traditional Cryosurgery

Traditional cryosurgery has been used to treat various cancers but often fails to effectively destroy tumors beyond the immediate frozen area. The unique ICIE approach enhances the efficacy of cryosurgery by enabling targeted delivery of therapeutic agents to both the primary tumor and distant metastatic sites. This dual action not only improves local treatment but also stimulates a systemic immune response against metastatic tumors without additional surgical intervention.

Development of Cold-Responsive Nanoparticles

The application outlines the creation of cold-responsive nanoparticles (CRNPs) designed to co-deliver chemotherapy and immunotherapy agents. These nanoparticles are engineered to ensure that both types of agents function effectively within the cytosol of cancer cells upon cold-triggered release. This innovative delivery system aims to improve safety and therapeutic outcomes in treating solid tumors.

Broader Implications and Future Applications

The ICIE method presents significant potential for advancing cancer treatment strategies. By effectively reversing the immunosuppressive TME, it could lead to robust immune responses against various cancer types, particularly metastatic breast cancer. Additionally, the technology can be adapted for other drug delivery systems, paving the way for enhanced therapeutic protocols in oncology and beyond.