Immune checkpoint blockade (ICB) therapy has the potential to revolutionize the treatment of multiple intractable cancers by boosting the immune system of patients to identify and eradicate tumors. One major challenge for the clinical application of ICB therapy is its low response rates, largely due to the low tumor immunogenicity of many solid tumors, thus only benefiting a small fraction of patients. The combination of ICB therapy with other therapeutic interventions, such as chemotherapy and radiation therapy, have only very limited success due to low clinical benefits and the possibility of inducing serious side effects. There is an unmet clinical need for efficient combination immunothe...

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Immune checkpoint blockade (ICB) therapy has the potential to revolutionize the treatment of multiple intractable cancers by boosting the immune system of patients to identify and eradicate tumors. One major challenge for the clinical application of ICB therapy is its low response rates, largely due to the low tumor immunogenicity of many solid tumors, thus only benefiting a small fraction of patients. The combination of ICB therapy with other therapeutic interventions, such as chemotherapy and radiation therapy, have only very limited success due to low clinical benefits and the possibility of inducing serious side effects. There is an unmet clinical need for efficient combination immunotherapy with high therapeutic efficacy and minimal adverse effects.

The goal of this project is to combine localized heating and free radical generation by magnetic nanoclusters with ICB to improve the therapeutic outcomes. The new class of nanotherapeutic agent we developed, composed of magnetic iron oxide nanoclusters (IONCs) and AAPH, can generate a high level of heat upon delivery into tumor and applying an alternating magnetic field (AMF), resulting in free radicals from AAPH decomposition. Magneto-immunotherapy, the combination of magnetic heating, free radical generation and ICB, will lead to an amplified anti-tumor immune response. Since magnetic field can penetrate human tissues with unlimited depth, this approach, is applicable to eradicate tumors in deep tissue noninvasively. This project aims to determine if localized hyperthermia and free radicals generated by IONC-AAPH under AMF will increase the efficiency of tumor eradication and improve the response to ICB therapy. Successful completion of this project will lead to a new combination immunotherapy with the potential to significantly improve therapeutic efficacy and patient response rates to immunotherapy, thus addressing an unmet clinical need.

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