A new treatment for canine B-cell lymphoma based on a recombinant single-domain antibody immunotoxin derived from Pseudomonas aeruginosa exotoxin A.

C5-PE38 immunotoxin shows promising preclinical efficacy against canine B-cell lymphoma.

Canine lymphoma represents a significant clinical challenge in veterinary oncology, with conventional chemotherapy often limited by lack of specificity, adverse effects, and treatment resistance. This study presents a novel immunotoxin-based therapeutic approach combining a recombinant single-domain antibody (sdAb) with PE38 exotoxin A. Researchers fused the C5 sdAb, previously developed for targeting canine B-cell lymphoma, with the PE38 toxin domain to create the C5-PE38 immunotoxin. In vitro testing against CLBL-1 canine lymphoma cells demonstrated potent cytotoxic activity (EC50 = 9.50 ± 0.04 μg/mL) through inhibition of protein synthesis and subsequent apoptosis. In vivo validation using CLBL-1 xenograft mouse models showed specific tumor uptake and significant tumor growth inhibition compared to control treatments. This research validates sdAb-PE38 immunotoxin scaffolds as a promising targeted anticancer strategy for canine tumors, offering potential advantages over conventional chemotherapy through enhanced specificity and reduced off-target toxicity. The findings contribute meaningfully to comparative oncology by demonstrating preclinical efficacy of this novel therapeutic class.

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