Recent Developments in Cancer Immunotherapy for Veterinary Patients

Cancer immunotherapy—the use of antibodies to treat tumors—has been established in human medicine for a couple of decades. However, recent advances have led to immunotherapy that is not only changing the standard of care for human cancer patients, but also moving to the forefront of cancer treatment options for veterinary patients. In a recent review article, Daniel Regan, DVM, and colleagues, Colorado State University, Fort Collins, Colorado discussed these breakthroughs, and highlighted how some of them may impact veterinary medicine.

According to the authors, one major breakthrough is the discovery that monoclonal antibodies can block certain immune checkpoint molecules and result in lasting tumor remissions in people with certain cancers. For example, the molecule PD-1, and its ligand PD-L1, represent a major checkpoint target for tumor immunotherapy. In addition, data from recent clinical trials have shown that treatment with monoclonal antibodies against PD-1 or PD-L1 can lead to meaningful tumor regression in certain patients with cancer. Interest in the potential use of these monoclonal antibodies in the treatment of cancer in dogs is growing, and initial studies assessing tumor biopsies have shown high levels of PD-L1 expression in several different canine tumor types.

Another breakthrough therapy that involves the administration of engineered T cells designed to target specific antigens on tumor cells has demonstrated significant tumor control and regression in clinical trials in human cancer patients. This approach typically involves collecting T cells from the patient (usually by surgical removal of a lymph node), expanding them in tissue culture, transfecting them (to attach antibodies directed against tumor antigen to the T cells, for example), and re-infusing them back into the patient. This form of therapy has resulted in dramatic control, and even cure, of certain refractory tumors in people.

Engineered monoclonal antibodies have also been developed against tumor or immune cell antigens for selective delivery to cancer cells, and numerous canine antibodies have been evaluated in phase 1 and 2 clinical trials in dogs with lymphoma. In particular, recent trials have reported significant increases in progression-free survival and overall survival time in dogs with B cell lymphoma that received canine anti-CD20 antibody and chemotherapy. Indeed, the United States Department of Agriculture (USDA) has now licensed a monoclonal canine anti-CD20 antibody for the treatment of canine B-cell lymphoma—they also granted a conditional license for use of a monoclonal canine anti-CD52 antibody for the treatment of dogs with T cell lymphoma.

Understanding of the key role of the innate immune system in regulating adaptive immune responses to cancer has also increased. Indeed, the authors include a recent study demonstrating efficacy of topical treatment with the TLR-7 ligand imiquimod combined with an autologous tumor cell vaccine in dogs with meningioma. Imiquimod has also been used to treat cats with squamous cell carcinoma in situ.

Many of the new advances in tumor immunotherapy for humans may soon find application in veterinary medicine, particularly as the costs of technologies continue to decrease, say the authors. “In the near future, tumor immunotherapy will likely become an accepted fourth arm of the cancer-fighting arsenal in veterinary medicine, along with surgery, chemotherapy, and radiation therapy.”

“Going forward, major challenges will include matching immune therapy most effectively to specific tumor types, and optimally incorporating immunotherapy into conventional treatment modalities,” the authors conclude.