Advances in therapeutic monoclonal antibodies: the structure, development strategies, and innovative forms

Authors

DOI:

https://doi.org/10.24959/nphj.26.209

Keywords:

immunoglobulins, monoclonal antibodies, novel therapeutics

Abstract

Aim. To comprehensively analyze the evolution of monoclonal antibody production technologies, ranging from classical hybridoma methods to modern transgenic platforms, with an assessment of their impact on the development of fully human, bispecific, and antibody-drug conjugates (ADCs).

Materials and methods. The study is based on a systematic literature review of the PubMed, Scopus, and Web of Science databases, as well as regulatory sources (FDA Purple Book, EMA Medicines database).

Results. The hybridoma technology developed in 1975 laid the foundation for the first monoclonal antibodies (mAbs); however, their murine origin resulted in high immunogenicity (HAMA). Evolution led to the development of chimeric and humanized mAbs with 95 % homology to human IgG to reduce HACA/HAHA responses. Fully human mAbs are currently generated using a phage display, the single B-cell isolation, and transgenic animals. Transgenic platforms (XenoMouse, HuMabMouse, VelocImmune, OmniAb) provide the in vivo maturation with a complete human repertoire. Bispecific antibodies (bsAb) minimize toxicity through the T-cell activation or pathway blockade, while antibody-drug conjugates (ADCs) deliver cytotoxic agents selectively.

Conclusions. The evolution of mAb production methods has made it possible to minimize immunogenicity and optimize the therapeutic efficacy of drugs. The introduction of bsAbs and ADCs has expanded the potential for selective immunotherapy. Future developments in the field are linked to the integration of artificial intelligence for the CDR design, the application of CRISPR/Cas9, and the engineering of multi-specific antibodies to overcome tumor resistance and treat neurodegenerative diseases.

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2026-03-31

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