Jianqin Lu, PhD
A New Nanotherapeutic Platform for Improving Response Rates to Immune Checkpoint Blockade Therapy in Colorectal Cancer
Immune checkpoints (IC) serve as a “brake” on immune systems to prevent immune responses from being too strong and thus detrimental to healthy cells. However, in tumors, blocking ICs unleashes antitumor immunity that can help eliminate cancer cells. While IC blockade (ICB) approaches have worked well for diverse cancers, response rates in colorectal cancer are only around 4%. Potent chemodrug Camptothecin (CPT) can enhance the effects of ICB therapy, but the drug’s poor solubility, short half-life, and systemic toxicities impede its clinical potential. I developed an innovative delivery platform by modifying CPT to form a nanotherapeutic that can address the drawbacks associated with CPT and fortify the responses of colorectal cancer tumors to ICB to prevent tumor recurrence. This project seeks to improve CPT nanotherapeutic systems via optimally codelivering an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor that overcomes tumor immune suppression for synergistic combination immunochemotherapy, which can further boost the clinical efficacy of ICB against colorectal cancer.
I am appreciative of the PhRMA Foundation support, which has allowed my lab to develop a safe and synergistic combination nanotherapeutic platform that not only can be translated into clinic for improved cancer therapy, but can also enhance the effectiveness of immune checkpoint therapy in colorectal cancer.