Current Review of Monoclonal Antibody Therapeutics in Small Animal Medicine

Abstract

Monoclonal antibody therapy has been a cornerstone of human healthcare for nearly four decades, effectively treating a wide range of diseases including cancers, autoimmune disorders, and inflammatory conditions. However, its application in veterinary medicine is a relatively recent development, offering a promising therapeutic approach for managing chronic diseases in small animals. Dogs and cats, like humans, suffer from chronic conditions such as cancer, arthritis, allergies, and chronic pain, which mAb therapy could potentially address. This review aims to explore the therapeutic potential of mAb therapy in small animal medicine, focusing on currently authorized products, including their mechanisms of action, clinical efficacy, and safety concerns. A comprehensive review of the literature was conducted to evaluate the use of mAbs in veterinary medicine, specifically in the treatment of chronic disorders. While mAb therapy has shown significant benefits in human healthcare, challenges remain in its application to veterinary practice, including safety concerns and the limited availability of approved products. Despite these challenges, mAb therapy holds great promise for improving the management of chronic diseases in animals, with future research and development potentially expanding its clinical use.

Keywords: atopic dermatitis; canine interleukin 31; chronic disorders; immunotherapy; lymphoma; mAb therapy; monoclonal antibody; nerve growth factor; osteoarthritis; pet animals.

Figure 1

A timeline of mAbs in veterinary medicine.

Figure 2

Composition of antibodies. Antibodies are large glycoproteins made of two heavy and two light chains, each with variable (VH, VL) and constant (CH, CL) domains (adapted from Masataka et al. [20]). The variable domain contains six hyper-variable loops (CDRs) that determine antigen specificity, while the constant domain is the same within an antibody isotype (e.g., IgG, IgM) but differs across isotypes. The Fc region of the constant domain activates immune responses. Murine mAbs come from cloned mouse B-lymphocytes, with most therapeutic mAbs being IgG isotypes. Chimeric mAbs combine murine variable regions with human constant regions, while humanized mAbs retain only the murine CDRs. Fully human, caninized, and felinized mAbs contain no murine sequences, and species-specific antibodies can be developed through processes like PETization, which aligns them with species-specific immunoglobulin libraries.

Figure 3

Lokivetmab’s mechanism in disrupting the itch cycle involves targeting canine interleukin-31 (IL-31), which plays a key role in the development of pruritus in dogs suffering from atopic dermatitis. By neutralizing IL-31, lokivetmab effectively reduces itching and helps minimize inflammatory skin lesions (Accessed 27 January 2025. https://todaysveterinarypractice.com/dermatology/advances-in-treatments-for-canine-atopic-dermatitis/).

Figure 4

NGF is the key player in pain perception and nervous system plasticity in osteoarthritis. Released by chondrocytes, NGF binds to TrkA on sensory fibers and immune cells, prompting the release of inflammatory mediators/autacoids, e.g., histamine and serotonin. The NGF/TrkA complex is transported to the dorsal root ganglion (DRG), increasing the expression of pain-related receptors and ion channels (e.g., TRPV1, ASIC, Nav), leading to peripheral sensitization. NGF also enhances production of pro-nociceptive neurotransmitters (SP, CGRP, BDNF), which, upon release, stimulate second-order neurons, potentially causing central sensitization. This process amplifies pain signaling from the periphery, e.g., joint to the brain [20]. Abbreviations: 5-HT, serotonin; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; ASIC, acid-sensing ion channel; BDNF, brain-derived neurotrophic factor; BR2, bradykinin receptor 2; Cav, calcium channel; CGRP, calcitonin gene-related peptide; DRG, dorsal root ganglion; K, potassium channel; Nav, sodium channel; NMDA, N-methyl-D-aspartate receptor; NGF, nerve growth factor; SP, substance P; TrkA/B, tropomyosin receptor kinase.

Figure 5

Inhibitors of PD-1 in cancer therapy work by blocking the PD-L1/PD-1 pathway, thereby reactivating the immune system’s anti-tumor response at two critical points: the cognitive phase in lymph nodes and the effector phase within the tumor microenvironment. These inhibitors include anti-PD-1 and anti-PD-L1 antibodies, which effectively disrupt the signaling that allows tumors to evade immune detection [55,57].