Introduction

Following immunotherapy, a minority of advanced-stage cancer patients develop immune responses resulting in durable tumor regression despite widespread metastasis. To expand this minority, we investigate external beam radiation (EBRT) and an intra-tumoral immunocytokine to create an in situ vaccine in one tumor microenvironment and combine this approach with systemic targeted radionuclide therapy (TRT) in order to propagate an abscopal effect at metastatic sites. We have documented durable responses in murine models and now present bridging data in companion dogs.

Methods

Five dogs with advanced-stage melanoma or osteosarcoma were included. A tumor-targeting alkylphosphocholine (NM600) that chelates radionuclides was used as a theranostic for serial diagnostic 86Y-NM600 PET/CT imaging of the primary tumor and metastatic sites. These images enabled Monte Carlo dosimetry calculations for subsequent delivery of therapeutic 90Y-NM600 to all sites. Concurrently, 8 Gy EBRT was delivered to the primary tumor followed by 3 daily intratumoral injections of hu14.18-IL2 immunocytokine. Adverse event (AE) data and biospecimens were collected.

Results

All metastatic tumors had differential uptake of 86Y-NM600 as evidenced by PET/CT and a minimum immunomodulatory dose of 2 Gy 90Y-NM600 was successfully delivered to all metastatic sites in 4 of 5 dogs. Treatments were well tolerated, and AEs were transient/low grade.

Conclusion

We confirmed tumor-selective uptake and the theranostic potential of NM600 to stage, create subject-specific dosimetry, and safely deliver TRT to metastatic sites in dogs with osteosarcoma and melanoma. Ongoing investigations include characterizing immunomodulatory and anti-tumor responses in larger cohorts along with investigations of higher TRT dosing and alternative radionuclides.

Funding Information

Funded in part by the following: U01CA233102-01 DHHS, PHS, NIH, and The Barbara A. Suran Comparative Oncology Research Institute.