Abstract
Immunotherapy has changed the oncology landscape during the last decade and become standard of care for several cancers. The combinations of immunotherapy with other treatment modalities are also being investigated. One of the challenges to investigate such combinations is to identify suitable mouse models for the pre-clinical experiments. In the past, we and other researchers showed that murine B16-F10 melanoma in C57Bl6 mice is refractory to treatment with immune checkpoint inhibitors. In this work we studied the suitability of an alternative syngeneic model, Cloudman S91 murine melanoma in DBA/2 mouse (DBA/2NCrl), to study the combination of immunotherapy targeting PD-1 and radioimmunotherapy targeting melanin. DBA/2 male and female mice were injected subcutaneously with 3–6 million Cloudman S91 cells. When the tumors reached ~150 mm3 volume, the animals were treated intraperitoneally with PBS (sham), h8C3 unlabeled (cold) antibody to melanin, immunotherapy with anti-PD-1 antibody, radioimmunotherapy with 213Bismuth (213Bi)-labeled h8C3 antibody, or several combinations of immunotherapy and radioimmunotherapy. Treatments with immunotherapy alone produced very modest effect on the tumor size, while combination therapy resulted in significant slowing down of the tumor growth, increased animal survival, and no decrease in animal body weight. We conclude that Cloudman S91 murine melanoma in DBA/2 mouse is a suitable model to evaluate combination of immunotherapy of melanoma with tangentially targeted treatments.
Highlights
Immunotherapy has changed the oncology landscape during the last decade and become standard of care for several cancers [1]
Metastatic melanoma was the first cancer for which immunotherapy with checkpoint inhibitors was approved by US FDA
In this work we evaluated the suitability of Cloudman S91 murine melanoma in DBA/2 mice for the studies combining immunotherapy and RIT
Summary
Immunotherapy has changed the oncology landscape during the last decade and become standard of care for several cancers [1]. Radioimmunotherapy (RIT) targets radiation at the molecular level utilizing radiolabeled monoclonal antibodies (mAbs) that bind to over-expressed, or uniquely cancer specific, antigens located either on the cancer cell membrane, or in the extracellular space of the tumor microenvironment These targeted radiopharmaceuticals can precisely deliver highly cytotoxic “internal radiation” to localized or systemic cancer deposits, while reducing potential side effects [5,6]. Several years ago we conducted a successful Phase 1 clinical trial in patients with metastatic melanoma using a murine antibody to melanin with an IgM isotype radiolabeled with a beta emitter 188Rhenium (188Re) [9]. This trial demonstrated safety and was indicative of the potential therapeutic efficacy of targeting melanin with radiolabeled antibodies. In this work we evaluated the suitability of Cloudman S91 murine melanoma in DBA/2 mice for the studies combining immunotherapy and RIT
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