Auburn College of Veterinary Medicine researcher developing novel immunotherapies to treat canine cancer with potential to improve human cancer therapeutics
By Jayne Hart
Throughout their careers, veterinarians care for many canine cancer patients and witness the devastating effects of this disease. Dr. Maninder Sandey is among these ranks. His experience treating dogs with cancer has turned into a determination to learn more about how cancer works at the molecular level while finding better ways to treat it that could help both dogs and people.
Cancer is one of the most common causes of death in humans and in the geriatric dog population. The mean survival time and overall survival for canine cancer patients are alarmingly low. However, naturally occurring cancers in dogs share many similarities with human cancer.
“By studying how treatments work in canine cancer patients, we can learn valuable information that can benefit both people and dogs,” said Sandey, associate professor of pathology in the Auburn College of Veterinary Medicine’s Department of Pathobiology. “Thus, our approach will provide dogs with cutting-edge immune therapies, while ensuring that people have access to treatments that are more likely to succeed.”
After earning his Doctorate in Veterinary Medicine, Sandey decided to pursue a doctorate in biomedical sciences from the Auburn University College of Veterinary Medicine. Coupled with his experience caring for canine cancer patients, his doctoral research experience has transformed into a dedication to developing new immunotherapies that could completely change the way cancer is fought in dogs by utilizing proven human cancer treatment methods.
“When I was performing my doctoral research, I had the amazing opportunity to study the intricate details of canine cancer,” Sandey recalled. “By studying the molecular mechanisms behind tumor growth and progression, I realized that immunotherapy, which uses the immune system to fight cancer, could be a promising approach in veterinary medicine. The idea of using the power of the immune system to target and eliminate cancer cells has already made a big impact in human medicine, and I believe it has the same potential to help our pet population.”
The human immune system plays a crucial role in fighting cancer, yet tumor cells are able to weaken immune-response and avoid detection. Immune checkpoint inhibitors (ICIs) are a type of treatment that can block tumor cells from circumventing the immune system and, in turn, help the immune system defeat cancer cells.
ICIs have been highly effective in treating different types of cancer and have even helped some patients achieve long-lasting remission after stopping treatment. However, they don’t work for everyone, and some patients can develop resistance to them. Sandey’s goal is to make these ICIs work better.
For the past three years, his research team has been actively engaged in a project specifically focused on the comprehensive characterization of an innovative bispecific platform funded through a National Institutes of Health (NIH) R15 grant from the National Cancer Institute. This highly effective form of treatment uses a bioengineered antibody that combines two antigens to improve its ability to overcome immune system limitations to mount an effective attack against cancer cells. The team’s novel treatment combines two approaches into a single therapeutic, which blocks an immune checkpoint called PD-1 and activates a protein called OX40.
Programmed cell death protein-1 (PD-1) is a T-cell protein that plays a crucial role in eliciting a balanced immune response by maintaining self-tolerance and minimizing harm to the host. Tumor cells often co-opt this pathway to suppress the antitumor immune response to evade elimination by T-cells.
In contrast, OX40, a potent immunostimulatory protein in the tumor necrosis factor receptor superfamily (TNFRSF), holds immense significance in the activation, proliferation and survival of T-cells. It is instrumental in generating a robust and effective anti-tumor immune response.
These OX40 agonists can work together with ICIs to boost the body’s natural defense against tumors to activate and even increase the number of T-cells. By using both ICIs and OX40 agonists, Sandey aims to enhance the immune system’s ability to fight cancer more effectively.
In most preclinical studies, researchers typically use two different antibodies to activate OX40 and block PD-1 in order to treat cancer. This approach may not be as effective due to the possibility of the two antibodies traveling to different parts of the body. To circumvent this separation, Sandey’s team has created a way to combine OX40 activation and PD-1 blocking into a single treatment.
This treatment utilizes nanobodies, the smallest naturally-occurring antibody fragments, which have emerged as a viable substitute for traditional antibody-based therapeutics and address antibody limitations. Nanobodies exhibit remarkable specificity and affinity for antigens, comparable to conventional antibodies. Due to their small size, they are highly valuable in molecular engineering aimed at development of bispecific constructs.
The immunotherapeutics developed by Sandey’s team target the critical control checkpoints in the immune response that allow the body to mount an effective anti-cancer attack. This team’s first patented drug strongly activates the immune cells by blocking immune-suppressive signaling. The treatment of canine cancer patients with these novel immunotherapeutics is expected to improve both mean survival times and overall patient survival.
Moreover, cancer in dogs has similar molecular characteristics, immune profiles and clinical presentation to human patients. Directly supporting the college’s One Health mission, these novel immunotherapeutics developed to treat canine patients have the potential to benefit both humans and animals, providing dogs with access to cutting-edge cancer treatments while ensuring humans receive treatments with higher rates of success.
The team’s primary focus revolves around assessing the therapeutic efficacy of the bispecific molecule against mucosal melanoma. Recognizing the similar role played by the immune system in various malignancies, Sandey’s plans are to evaluate the clinical effectiveness of the molecule in other types of cancer as well, including pediatric osteosarcoma and breast cancer. A clinical trial is expected soon for enrollment of canine cancer patients and will be conducted by Auburn’s Bailey Small Animal Teaching Hospital.
“This is a unique approach that hasn’t been tried before in lab studies. What makes our study even more special is that we are testing this new treatment in dogs with cancer,” said Sandey. “Not only does this approach have the potential to help people, it also provides a new treatment option for our furry friends, improving their quality of life.”