Research Study Update: Enhancing natural anti-tumor immune responses during chemotherapy

AKC Canine Health Foundation Grant 1703-A
Principal Investigator: Dr. Annette N. Smith, DVM; Auburn University

Study supports the use of a chlorambucil for chemotheraphy

In dogs with cancer, suppressor T cells (Treg) are believed to prevent the elimination of cancer by suppressing killer immune cells. Dogs with cancer have significantly higher numbers of Treg when compared to healthy dogs because of stimuli secreted by the cancer. Increased numbers of Treg result in a decreased immune response to tumors and are associated with decreased survival in dogs with cancer. The goal of this study is to evaluate the effect of metronomic (daily, low dose) chlorambucil on Treg and killer immune cells using flow cytometry. The hypothesis of this study is that chlorambucil will significantly decrease the number of Treg and decrease the immune cell/Treg ratio. Confirmation of this hypothesis will prove that chlorambucil is an effective treatment; thus, potentially enhancing a dog’s natural ability to mount an anti-tumor response.

The data from this study demonstrate that metronomic chlorambucil significantly decreases the number of Tregs after one month of treatment in dogs with soft tissue sarcomas. This treatment modality may improve survival times by significantly decreasing the number of Tregs in cancer bearing dogs. This information demonstrates that metronomic chlorambucil at a dose of 0.1mg/kg is effective and can be utilized instead of another form of chemotherapy - metronomic cyclophosphamide.  Cyclophosphamide can have the side effects of bladder pain and blood in the urine. This study supports the use of metronomic chlorambucil instead of cyclophosphamide to eliminate the risk of those side effects. Oftentimes, the dosing regimen for chlorambucil is better for smaller dogs (i.e. dogs under 10 kg). Therefore, the information provided in this study is beneficial for small breed dogs as well as larger dogs. Future research evaluating the effects of chlorambucil on angiogenesis (a process necessary for tumor growth) would be beneficial to completely confirm its use in metronomic chlorambucil. Additionally, it would be interesting to evaluate the effects of metronomic chlorambucil at lower doses because a lower dose would be more cost effective for the dog owner.