EXTH-28. DEVELOPING A NOVEL INJECTABLE IMMUNOTHERAPEUTIC GEL FOR ENCAPSULATION OF NATURAL KILLER CELLS FOR POST-SURGICAL GLIOBLASTOMA TREATMENT

Abstract Malignant brain tumors are one of the leading causes of death among all cancers. Approximately 40,000 people are diagnosed with malignant brain tumors every year. Among these patients, 15,000 cases are glioblastoma (GBM) with a very poor prognosis; even after aggressive surgical resection and adjuvant chemo/radiotherapy, the median survival is only 14.6 months. The major reason for poor prognosis is the blood-brain barrier, which prevents therapeutic agents from reaching the target area. Therefore, there are only a few choices of drugs available for brain tumor treatment. To date, temozolomide (TMZ) and the Gliadel wafer have been clinically used as standard chemotherapy agents after brain tumor resection. However, drug resistance to TMZ and the poor drug diffusion rate of the Gliadel wafer still result in ineffective suppression of residual cancer cells. To overcome the above-mentioned difficulties in clinical brain tumor treatment, in situ self-crosslinking multifunctional hydrogels was developed to carry natural killer cells (NK cells) and radiosensitizers as a novel brain tumor treatment system. Unlike traditional hydrogels catalyzed by pH value or temperature, this new system is stable and consistent as an immune cell carrier. We used fibrinogen, thrombin, and alginic acid as the backbone of the in situ self-crosslinking hydrogel, tested the properties of the synthesized hydrogel, and analyzed the gel-formation time and swelling rate. The release rate of NK cells was also examined. In a brain tumor animal model, the use of hydrogel-NK cells significantly inhibited tumor proliferation and prolonged animal survival time. In conclusion, this therapeutic hydrogel carrying NK cells can serve as a novel post-operation adjuvant therapeutic tool for malignant brain tumors.