In this post, Yoon Yeo, the Lillian Barboul Thomas Professor of Industrial and Molecular Pharmaceutics in the College of Pharmacy, and a member of the Purdue Institute for Cancer Research, the Purdue Institute for Drug Discovery, and the Purdue Institute for Inflammation, Immunology and Infectious Disease, discusses her research “Timely administration of drug combination improves chemoimmunotherapy of an immune-cold tumor” which was recently published in the Journal of Controlled Release with the support of the the National Institutes of Health (NIH R01 CA232419 and NIH R01 CA258737). The authors also acknowledge the support from the Purdue Institute for Cancer Research, and NIH grant P30 CA023168.
What did you want to know?
We previously reported that a nanoparticle complex, called IMmunoActive complex (IMAX), composed of an anticancer drug, polymer, and immune modulator, can activate immune activity against solid tumors. In many mouse models, a single treatment led to strong responses, resulting in tumor-free survival. However, in some cases, tumors regrew after the initial response. Our goal is to investigate the mechanisms of resistance and develop therapeutic strategies to overcome the resistance.
What did you achieve?
IMAX-treated tumors were initially infiltrated by innate immune cells, as expected based on the activity of each component. However, the immune cell population began to decline five days after treatment, indicating that the immunostimulatory effect was transient and insufficient to sustain the antitumor response in resistant tumors. Notably, administering an additional immunostimulatory treatment when the immune cell population peaked, but not before or after, significantly enhanced the antitumor response, leading to complete regression in 50% of the tumors by day 126 (the duration of observation) and a median survival of 109 days. Among the tumor-free survivors, 67% successfully rejected a live tumor rechallenge.
What is the impact of this research?
Our study demonstrates that IMAX treatment effectively activates antitumor immune responses. When combined with an additional immunostimulatory treatment at an optimal interval, IMAX showed a significant improvement in antitumor efficacy compared to other studies using the same tumor model. These findings underscore the critical impact of treatment timing on therapeutic outcomes.