Hypo-fractionated radiation, magnetic nanoparticle hyperthermia and a viral immunotherapy treatment of spontaneous canine cancer

Abstract

It has recently been shown that cancer treatments such as radiation and hyperthermia, which have conventionally been viewed to have modest immune based anti-cancer effects, may, if used appropriately stimulate a significant and potentially effective local and systemic anti-cancer immune effect (abscopal effect) and improved prognosis. Using eight spontaneous canine cancers (2 oral melanoma, 3 oral amelioblastomas and 1 carcinomas), we have shown that hypofractionated radiation (6 x 6 Gy) and/or magnetic nanoparticle hyperthermia (2 X 43°C / 45 minutes) and/or an immunogenic virus-like nanoparticle (VLP, 2 x 200 μg) are capable of delivering a highly effective cancer treatment that includes an immunogenic component. Two tumors received all three therapeutic modalities, one tumor received radiation and hyperthermia, two tumors received radiation and VLP, and three tumors received only mNP hyperthermia. The treatment regimen is conducted over a 14-day period. All patients tolerated the treatments without complication and have had local and distant tumor responses that significantly exceed responses observed following conventional therapy (surgery and/or radiation). The results suggest that both hypofractionated radiation and hyperthermia have effective immune responses that are enhanced by the intratumoral VLP treatment. Molecular data from these tumors suggest Heat Shock Protein (HSP) 70/90, calreticulin and CD47 are targets that can be exploited to enhance the local and systemic (abscopal effect) immune potential of radiation and hyperthermia cancer treatment.

Nanoparticle-Based Drug Delivery in Cancer Therapy and Its Role in Overcoming Drug Resistance

“…They have been shown to demonstrate high efficacy in chemotherapy and gene therapy for cancer treatment ( Basoglu et al, 2018 ; Mandriota et al, 2019 ). Furthermore, magnetic hyperthermia using MNPs can achieve thermal ablation of tumors, which offers alternative cancer treatment ( Hoopes et al, 2017 ; Legge et al, 2019 ).…”

The Abscopal Effect: Could a Phenomenon Described Decades Ago Become Key to Enhancing the Response to Immune Therapies in Breast Cancer?

“…In a rat model magnetic seed-mediated hyperthermia led to regression of a nontreated lesion and a significant increase in CD8 + cells [45]. Other experiments including different tumors and treatment with radiation and magnetic seed-mediated hyperthermia with or without the application of virus-like-nanoparticles showed local and distant tumor responses with a significantly better response than expected by radiation alone, suggesting an effective immune response [46]. In a trial investigating whether magnetic iron oxide nanoparticle hyperthermia (MION-HT) can enhance abscopal effects with radiotherapy and immune checkpoint inhibitors in a triple-negative breast cancer mouse model, the combination of local irradiation, MION-HT, and PD-1 or CTLA-4 inhibitors led to a decrease in the local tumor burden and increased CD3 + T lymphocytes.…”

“…In a rat model magnetic seed-mediated hyperthermia led to regression of a nontreated lesion and a significant increase in CD8 + cells [45]. Other experiments including different tumors and treatment with radiation and magnetic seed-mediated hyperthermia with or without the application of virus-like-nanoparticles showed local and distant tumor responses with a significantly better response than expected by radiation alone, suggesting an effective immune response [46].…”

Exploring the Potential Utility of Pet Dogs With Cancer for Studying Radiation-Induced Immunogenic Cell Death Strategies

“…While existing aggregate data for validating radiation-induced ICD and abscopal activities in pet dogs with cancer remains limited, experimental data is emerging to support the prospective evaluation of hypofractionated radiation therapy for augmenting immune responses. Recently, combinatorial strategies inclusive of ionizing radiation, hyperthermia, and intratumorally delivered virus-like nanoparticle-based therapies have been evaluated in canine OMM, and demonstrate the capacity to elicit immunogenic changes within the localized tumor microenvironment including the promotion TILs into the primary tumor (121, 122). In another investigation conducted in dogs with OMM, abscopal effects were documented in dogs treated with a combination of localized radiation therapy, intratumoral CpG ODN, and an indolamine-2,3-dioxygenase inhibitor (123).…”