2021 Annual Meeting
Design of Novel Tumor-Binding Cytokine Immunotherapies for the Intratumoral (IT) Treatment of Solid Tumors
Conventional therapies to treat solid tumors can inflict many complications on the patientâs body due to a lack of tumor-killing specificity. To avoid this risk, cancer immunotherapy that activates the patientâs own immune system to selectively fight cancer is a better alternative. One such immunostimulant currently being investigated in clinical trials is a type of cytokine called GMCSF (granulocyte macrophage-colony-stimulating factor). Local injection of GMCSF can recruit and activate antigen-presenting cells (dendritic cells) into the tumor lesions, thereby initiating anti-tumor responses. However, the main limitation of local GMCSF treatment is its lack of retention within the tumor tissue leading to systemic toxicity in patients. In order to address this problem, this research focuses on the design of an engineered-GMCSF (eGMCSF) that exhibits superior retention and immune stimulation at the injection site, thereby providing a safer and more efficacious treatment strategy for solid tumors. This is attained by fusing GMCSF with a tumor binding peptide that is designed to bind to tumor ECM (extracellular matrix) components, such as hyaluronic acid (HA) and Fibronectin. The efficacy of the eGMCSF is investigated by testing its tumor binding capabilities using an in vitro tumor model. Additionally, the immunological capabilities of eGMCSF are studied by elucidating the proliferative effect on dendritic cells (DCs).