Program Information
Hyperthermia-Driven Immunotherapy Using Non-Invasive Radiowaves
R Serda1*, D Savage2 , S Corr3 , S Curley4 , (1) ,,,(2) Baylor College of Medicine, Houston, Texas, (3) Baylor College of Medicine, Houston, Texas, (4) Baylor College of Medicine, Houston, Texas
Presentations
TH-C-17A-11 Thursday 10:15AM - 12:15PM Room: 17APurpose:
The sad truth is that cancer is blamed for the death of nearly one in four people in the US. Immunotherapy offers hope for stimulating cancer immunity leading to targeted killing of cancer cells and a preventative measure for cancer recurrence. Unfortunately, the clinical efficacy of immunotherapy has not yet been established, however novel approaches are being developed, including combining immunotherapy with traditional chemotherapy, radiotherapy or thermal therapy. Therapeutics such as radiofrequency (RF) ablation and select chemotherapeutics induce mild anti-cancer immune responses. This project seeks to enhance the immune responses stimulated by these agents by co-delivery of nanoparticle-based chemotherapeutics and immune modulators in the presence of RF induced hyperthermia.
Methods:
A 4T1 mouse model of breast cancer is used to test the ability of RF waves to enhance accumulation of nanoparticles in tumor tissue by increasing blood flow and extravation of nanoparticles from hyperpermeable vessels. Images of particle and cell trafficking in the tumor are captured using an integrated RF and confocal imaging system, and tumor growth is monitored by tumor bioluminescence and caliper measurements.
Results:
Here we demonstrate enhanced intratumoral blood flow induced by non-invasive RF waves and an increase in nanoparticle accumulation in the tumor. IL-12 is shown to have powerful anti-tumor effects leading to tumor regression and the release of Th1-biased cytokines. Doxorubicin nanoparticles combined with adjuvant nanoparticles exhibited superior anti-tumor effects to single agent therapy.
Conclusion:
RF therapy combined with nanotherapeutics is a promising approach to enhance the delivery of therapeutics to the tumor and to stimulate a tumor microenvironment that supports the development of cancer-specific immune responses.
Funding Support, Disclosures, and Conflict of Interest: This research was supported by the National Institute of Health grant numbers U54 CA143837 and U54 CA151668, and the Kanzius Foundation.
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