Monoclonal Antibodies for the Treatment of Ocular Diseases

Abstract

Monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy, offering unprecedented specificity and diverse mechanisms to combat malignant cells. These biologic agents have emerged as a cornerstone in targeted cancer treatment, binding to specific antigens on cancer cells and exerting their therapeutic effects through various mechanisms, including inhibition of signaling pathways, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). The unique ability of mAbs to engage the immune system and directly interfere with cancer cell function has significantly enhanced the therapeutic armamentarium against a broad spectrum of malignancies. mAbs were initially studied in oncology; however, today, treatments have been developed for eye diseases. This review discusses the current applications of mAbs for the treatment of ocular diseases, discussing the specificity and the variety of mechanisms by which these molecules exhibit their therapeutic effects. The benefits, drawbacks, effectiveness, and risks associated with using mAbs in ophthalmology are highlighted, focusing on the most relevant ocular diseases and mAbs currently in use. Technological advances have led to in vitro production methods and recombinant engineering techniques, allowing the development of chimeric, humanized, and fully human mAbs. Nowadays, many humanized mAbs have several applications, e.g., for the treatment of age-related macular disease, diabetic retinopathy, and uveitis, while studies about new applications of mAbs, such as for SARS-CoV-2 infection, are also currently ongoing to seek more efficient and safe approaches to treat this new ocular disease.

Keywords: age-related macular degeneration; diabetic retinopathy; monoclonal antibodies; ocular diseases; uveitis.

Figure 1

Mechanisms of action for therapeutic monoclonal antibodies (mAbs) in cancer treatment: (1) Inhibition of signaling pathways, targeting key proteins such as AKT (Protein Kinase B) and ERK (Extracellular Signal-Regulated Kinase). (2) Antibody-Dependent Cellular Cytotoxicity (ADCC), where mAbs engage Fc-Gamma Receptors (FcγRIII, FcγRI) on immune effector cells, leading to the destruction of cancer cells. (3) Complement-Dependent Cytotoxicity (CDC), where mAbs activate the complement cascade through C1q, leading to the formation of the Membrane Attack Complex (MAC) and cell lysis. (4) Antibody-Dependent Cellular Phagocytosis (ADCP), where mAbs facilitate the recognition and subsequent phagocytosis of cancer cells by macrophages and other phagocytic cells (modified after Rodríguez-Nava [4]).

Figure 2

Schematic description of the four main types of mAb compositions for therapeutics: 1—general mAb structure; 2—mouse mAb; 3—humanized mAb; 4—chimeric mAb; 5—human mAb. Pink: mouse sequences; green: human sequences; yellow rectangles: areas of glycosylation [own drawing].

Figure 3

A comprehensive depiction of the various causal factors of hyperglycemia, AGEs, and oxidative stress (OS) across the various stages of diabetes mellitus. A “micro” metabolic memory, which operates at the mitochondrial level, is thought to liberate the effects of AGEs from the constraints of chronic hyperglycemia. Conversely, a “macro” metabolic memory emerges from the prolonged interplay between oxidative stress and glycation at the tissue and vessel levels, serving as a link between damage to both large and small blood vessels. AGEs stands for advanced glycation end products, mtDNA for mitochondrial DNA, OS for oxidative stress, PKC for protein kinase C, and RCPs for respiratory chain proteins; ↑, increase, ↓ decrease [own drawing].