Canine CAR-T Cell Therapy

Overview

Dogs are a man’s best friend, and it is always upsetting for dog owners when their beloved dogs are diagnosed with fatal illnesses with no hope of a cure to treat them safely and successfully. B-cell lymphoma is the most prevalent hematological neoplasms in veterinary medicine. Based on an estimated 75 million canines in the United States, 16,000-80,000 new cases of canine lymphoma are detected each year. When they are diagnosed with late-stage or terminal illness, there are sometimes no treatment options available.

Focusing on canine B-cell lymphoma in particular, the standard of care for dogs with high-grade lymphoma over the last 35 years has ranged from single agent protocols to combination chemotherapy regimens of variable duration. Monoclonal antibody therapy and adoptive represent a novel therapeutic approach for cancer immunotherapy. The adoptive transfer of autologous T cells that are genetically modified to express a CD19-specific chimeric antigen receptor (CD19 CAR-T cells) has produced a high rate of complete remission in clinical trials for human B-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia and non-Hodgkin lymphoma.

Applications in Veterinary Oncology: A Need for New and Innovative Therapies in Canine B-cell Lymphoma

Each year, more than 4.2 million canines in the United States are diagnosed with cancer. The most frequent canine malignancies recognized and managed include lymphoma, mast cell tumor, osteosarcoma, soft tissue sarcoma, hemangiosarcoma, and melanoma.

There is abundant recent literature highlighting the pathologic, biologic, immunophenotypic, genetic and treatment response similarities between human and canine lymphoma. The most common subtype examined with genomic profiling in veterinary medicine is Diffused large B-cell Lymphoma (DLBCL). Utilizing immunohistochemistry and gene expression profiling, similar profiles were noted between human and canine DLBCL, and certain markers were able to separate the canine DLBCL cases into 2 groups with significantly different clinical outcomes. 

Provided this expanding body of data supporting the parallels between the most common types of human and canine lymphoma, the opportunities for therapeutic development on one specie to inform and progress that in the other species will only continue to grow.

The majority of canine cancer treatments rely on the use of human generic chemotherapeutics. The clinical responses to these therapeutics for the most common canine cancers have remained static for the past 10-20 years.

Focusing on canine B-cell lymphoma in particular, the standard of care for dogs with high grade lymphoma over the last 35 years has ranged from single agent protocols to combination chemotherapy regimens of variable duration. However, the response to chemotherapy is often sub-optimal with recurrent or refractory disease representing a significant clinical challenge. 

Immuno-oncology innovations are starting to make their way to veterinary oncology but remain limited with extremely sparse supporting data. 

General Process Workflow

Workflow of Chimeric Antigen Receptor (CAR) T cell Therapy in veterinary medicine

References

  1. Car-T cell therapy for dogs with CD20 positive B cell lymphoma. College of Veterinary Medicine. (n.d.). https://vetmed.umn.edu/departments/centers-and-programs/clinical-investigation-center/current-clinical-trials/car-t-cell#:~:text=Canine%20B%2Dcell%20lymphoma%20resembles,and%20key%2C%20and%20destroy%20it. 
  2. T;, S. O. M. (n.d.). Optimization of canine CD20 chimeric antigen receptor T cell manufacturing and in vitro cytotoxic activity against B-cell lymphoma. Veterinary and comparative oncology. https://pubmed.ncbi.nlm.nih.gov/32329214/ 
  3. Zhang, S., Kohli, K., Black, R. G., Hayes, B., Miller, C., Maeda-Whitaker, M., Schroeder, B., Abrams, K., Seguin, B., Gottschalk, S., Moore, P., Torok-Storb, B., & Pollack, S. (2020, November 1). 139 establishment of canine car T cells treatment model for solid tumor immunotherapy development. Journal for ImmunoTherapy of Cancer. https://jitc.bmj.com/content/8/Suppl_3/A84