INJECTABLE NANOPARTICLE-BASED HYDROGELS FOR LOCAL CANCER IMMUNOTHERAPY
When properly deployed, the immune system can render deadly pathogens harmless, eradicate even metastatic cancers, and provide long-lasting protection from diverse diseases. However, realizing these remarkable capabilities is inherently risky, as disruption to immune homeostasis can lead to dangerous complications and autoimmune disorders. While current research is continuously expanding the arsenal of potent immunotherapeutics, there is a technological gap when it comes to controlling when, where, and how long these drugs act on the body.
My postdoctoral research focused on ways to close this gap through the development of macroscopic, immuno-modulatory biomaterials that are composed from nanoparticle building blocks. Using quantitative PET imaging and multiplexed cytokine analyses, I demonstrated that injectable hydrogels significantly alter the pharmacokinetics and pharmacodynamics of potent immunostimulatory drugs in vivo. These hydrogels were able to significantly enhance on-target exposure to immunostimulatory drugs, while reducing off-target exposure throughout the body. These changes in pharmacokinetics corresponded to changes in proinflammatory cytokine levels, with our localized therapies inducing more effector cytokines in the tumor draining lymph node than clinical standard approaches. Importantly from a safety perspective, our localized approach significantly reduced inflammatory cytokine levels found in circulation, which are associated with problematic immunotherapy-related side effects. Overall, delivering immunostimulatory drugs with nanoparticle-based hydrogels improved the safety and efficacy of treatment, and synergized with other forms of immunotherapy to overcome a difficult-to-treat model of melanoma. My future research endeavors will seek to further refine the capabilities of local delivery vehicles for immunotherapy by exploring multi-drug and scheduled drug release.
Read more about this research here:
Correa S, Gale EC, Mayer AT, Xiao Z, Liong C, Klich JH, Brown RA, Meany E, Saouaf O, Maikawa CL, Grosskopf AK, Mann JL, Idoyaga J, Appel EA. Injectable Nanoparticle-Based Hydrogels Enable the Safe and Effective Deployment of Immunostimulatory CD40 Agonist Antibodies. bioRxiv. 2021:2021.06.27.449987.