Monoclonal Antibodies in Human Therapeutics: A Critical Appraisal of Mechanisms, Clinical Evidence, Safety and Access

Abstract

Monoclonal antibodies have become one of the largest classes of prescription medicine, with more than two hundred marketed products spanning oncology, immune-mediated inflammatory disease, cardiovascular and neurological disorders, haematology and infectious disease. The scale of this expansion has produced a literature that is extensive but fragmented, organised largely by target or disease and more descriptive than evaluative. This critical narrative review examines therapeutic monoclonal antibodies and the principal engineered formats derived from them, covering discovery and engineering platforms, mechanisms of action and pharmacology, clinical evidence across therapeutic domains, safety and immunogenicity, and the manufacturing, biosimilar and access questions that determine real-world use. Literature was identified through structured searching of open scholarly databases and trial registries, with verification of bibliographic metadata and appraisal of each source according to criteria appropriate to its design. Four themes emerge. Mechanistic accounts are more confident than the human evidence supporting them, particularly for fragment crystallisable-dependent effector killing, where the clinical contribution remains unquantified for nearly every marketed product. Pivotal evidence depends heavily on surrogate end points, single-arm registration and follow-up that is short relative to the duration of exposure, which limits inference about comparative and durable benefit. Safety signals are better understood when classified by source of harm, since target-related effects are largely foreseeable from target biology whereas format-related and class-related effects have proved less predictable. Access is highly unequal, with consumption differing by roughly two orders of magnitude between lower-middle-income and high-income economies. Several conclusions are secure, including the reproducible benefit of neutralising and receptor-blocking antibodies, the population-level effectiveness of long-acting respiratory syncytial virus prophylaxis, and the safety of biosimilar switching for the products studied. Others remain unresolved, including whether small clinical effects of amyloid-directed antibodies accumulate into meaningful benefit and whether computational antibody design will yield molecules that succeed in patients. Progress on delivery, durability, measurement standardisation and equitable distribution, rather than further expansion of the molecular repertoire, is likely to determine the additional health benefit this class delivers.