Safety and biologic activity of a canine anti‐CD20 monoclonal antibody in dogs with diffuse large B‐cell lymphoma

Abstract

BackgroundTo explore the safety and utility of combining low dose single‐agent doxorubicin with a canine specific anti‐CD20 monoclonal antibody (1E4‐cIgGB) in client owned dogs with untreated B‐cell lymphoma.AnimalsForty‐two client‐owned dogs with untreated B‐cell lymphoma.MethodsA prospective, single arm, open label clinical trial of dogs with B‐cell lymphoma were enrolled to receive 1E4‐cIgGB and doxorubicin in addition to 1 of 3 immunomodulatory regimens. B‐cell depletion was monitored by flow cytometry performed on peripheral blood samples at each visit.ResultsDogs demonstrated a statistically significant depletion in CD21+ B‐cells 7 days following the first antibody infusion (median fraction of baseline at 7 days = 0.04, P < .01) that persisted throughout treatment (median fraction of baseline at 21 days = 0.01, P < .01) whereas CD5+ T‐cells remained unchanged (median fraction of baseline at 7 days = 1.05, P = .88; median fraction of baselie at 7 days = 0.79, P = .42; Figure 1; Supplemental Table 3). Recovery of B‐cells was delayed, with at Day 196, only 6/17 dogs (35%) remaining on the study had CD21+ counts >0.5 of baseline, indicating sustained B cell depletion at 4+ months after the final treatment. 1E4‐cIgGB was well tolerated with only 1 dog exhibiting a hypersensitivity event within minutes of the last antibody infusion.ConclusionsThe canine 1E4‐cIgGB anti‐CD20 monoclonal antibody is apparently safe when administered with doxorubicin and effectively depletes B‐cells in dogs with DLBCL.

Editorial: New insights in veterinary cancer immunology

“…Cancer immunology explores the mechanisms by which the immune system can detect and destroy cancer cells, as well as how tumors evade immune surveillance ( 3 ). Research in veterinary cancer immunology has revealed that, similar to humans, animals' immune systems can recognize cancer-specific antigens and mount a response ( 1 , 4 ). However, tumors often develop strategies to suppress the immune response, such as producing immunosuppressive cytokines or recruiting regulatory T cells that inhibit anti-tumor activity.…”

“…Recent advancements in veterinary cancer immunology include the development of novel immunotherapeutic approaches. These include cancer vaccines that stimulate the immune system to recognize and attack tumor cells, monoclonal antibodies that target specific cancer antigens, and checkpoint inhibitors that block proteins used by cancer cells to evade immune detection ( 4 , 6 , 7 ). Clinical trials in veterinary medicine have shown promising results, particularly in treating canine cancers like lymphoma ( 4 ) and osteosarcoma ( 8 ).…”

“…These include cancer vaccines that stimulate the immune system to recognize and attack tumor cells, monoclonal antibodies that target specific cancer antigens, and checkpoint inhibitors that block proteins used by cancer cells to evade immune detection ( 4 , 6 , 7 ). Clinical trials in veterinary medicine have shown promising results, particularly in treating canine cancers like lymphoma ( 4 ) and osteosarcoma ( 8 ). These therapies not only improve the prognosis and quality of life for animals but also provide valuable insights that can translate to human oncology.…”