Lymphoma—Dogs and Humans
Approximately 40 percent of people with diffuse large B cell lymphoma (DLBCL) still die of the disease, and even those cured experience long-term side effects from chemotherapy. While small-molecule inhibitor drugs have made an impact, immunotherapy, specifically using antibodies like anti-CD20, has had the most profound effect on treatment strategies and long-term outcomes. Still, urgent work needs to be done to achieve better disease control.
Kristy L. Richards, Biomedical Sciences, College of Veterinary Medicine; Hematology and Medical Oncology, Weill Cornell Medicine, suggests that this progress can be made by studying DLBCL in dogs already suffering with the disease.
The molecular and genetic phenotype of canine DLBCL often resembles the activated B-cell state associated with aggressive DLBCL in people. Moreover, specific genetic changes and pathway aberrations are conserved across dogs and people with DLBCL, supporting the notion that the canine disease can be used as a relevant, spontaneous large-animal model. Working with Cheryl A. London (Tufts University), Richards is using dogs with spontaneous naive DLBCL to rapidly evaluate small-molecule and immunotherapy combination approaches, with the ultimate goal of identifying the most effective combination to move forward in human patients with DLBCL.
The team is also interrogating correlative biomarkers based on RNA sequencing of tumor samples from dogs enrolled in the trials and developing signatures that can be used to predict not only response to therapy but long-term remission and survival. The data generated will create a framework for effectively leveraging information from immunotherapeutic trials in canine patients to develop chemo-free strategies that improve human outcomes. NIH Award Number: 1U01CA224153-01