Treating Deadly Breast Cancer with a Plant Virus-based Immunotherapy

Canine veterinary patient
Dartmouth Cancer Center researchers Hugo Arias-Pulido, PhD, and Steven N. Fiering, PhD, are using the ability to treat natural cancer in veterinary dogs as an opportunity to study and develop the same immunotherapy for human cancer patients.

These biomarkers could be used to monitor response to this therapy in humans in future studies.

Hugo Arias-Pulido, PhD

Dogs, like humans, are affected by cancer. The ability to treat naturally occurring tumors in veterinary patients provides a unique opportunity to find therapies that could also help human cancer patients. One of these diseases, inflammatory breast cancer (IBC) is a rare but deadly type of human breast cancer.

Female dogs can develop a similar inflammatory mammary cancer (IMC) that occurs in dogs outside of the United States, due to lower rates of spaying young female dogs. Both cancers lack effective therapies, and the aggressiveness of this disease generally rules out surgery.

Powerful plant virus

Now, researchers from Dartmouth and Dartmouth Cancer Center are studying new immunotherapies for human inflammatory breast cancer, by evaluating efficacy, safety and clinical benefit of cowpea plant mosaic virus (CPMV) nanoparticle injections into tumors of companion dogs with IMC. This multi-nation collaboration was coordinated by Hugo Arias-Pulido, PhD, senior scientist in the Fiering Laboratory, and Steven Fiering, PhD, a member of Dartmouth Cancer Center’s Immunology and Cancer Immunotherapy Research Program.

Injection of CPMV immunotherapy into tumors was the only treatment provided to five female companion dogs affected with inflammatory mammary cancer. Results were several-fold:

  • The therapy generated strong anti-tumor immune responses.
  • Treatment was safe without any apparent adverse effects.
  • Treatment resulted in better quality of life.
  • The therapy significantly extended survival of the treated dogs when compared to untreated dogs.

While surgery is not an expected option with this very aggressive cancer, CPMV treatment also stimulated anti-tumor immune responses that reduced injected tumors enough to enable surgery in two of the dogs. 

“This is exciting because the tumor reduction and improvement in survival has not been observed in IMC patients with a single monotherapy as we observed with the CPMV nanoparticles,” says Arias-Pulido. “The potential to collect tumor and blood samples before and after treatment provides a unique opportunity to study the immune response induced by CPMV nanoparticles and identify immune cells and molecular events associated with the response. These biomarkers could be used to monitor response to this therapy in humans in future studies.”

Clinical development

Early on in the discovery process, Fiering and colleague Nicole F. Steinmetz, PhD, director of the UC San Diego Center for Nano-ImmunoEngineering, founded Mosaic ImmunoEngineering, Inc.

CPMV inset
Though it does not infect mammals, the cowpea mosaic plant virus is recognized by and strongly stimulates the immune system to attack and often eliminate cancerous tumors. Photo credit: Nicole Steinmetz.

In March of this year, the co-founders and their team both published their most recent veterinary trial results in Journal for ImmunoTherapy of Cancer, and received US Patent and Trademark Office approval to protect the technology behind Mosaic’s lead immuno-oncology product candidate. The patent will allow the team to continue clinical development of this first-in-class immune stimulant.

Future studies include expanding this new approach to a larger number of IMC dog patients, with the ultimate goal of introducing CPMV immunotherapy as a new treatment for human patients with breast cancer and other solid tumors. These study results and new patent open doors to a groundbreaking therapy for patients who lack specific therapies.

Steven N. Fiering, PhD, is a member of the Immunology and Cancer Immunotherapy Research Program at Dartmouth and Dartmouth Cancer Center and a Professor of Microbiology and Immunology at the Geisel School of Medicine at Dartmouth. His research interests include developing clinically useful in situ vaccination approaches to generate therapeutic anti-tumor immunity.

Hugo Arias-Pulido, PhD, is the senior scientist in the Steven Fiering Laboratory, and lead author of the study. His research interests include developing optimal animal models to evaluate efficacy of novel agents, including immunotherapeutic compounds.