Monoclonal Antibodies (mAbs) – the magic bullets: A review of therapeutic applications and its future perspectives

D. Suryaprabha*

Senior Executive-Clinical Research, Kauvery Hospitals, India

*Correspondence: Tel.: +91 98414 86267; email: [email protected]

Abstract

Background: The objective of this paper is to present an overview of the ongoing development of specific Monoclonal Antibodies and discuss their therapeutic applications and future prospects.

Methods: Among the emerging modes of therapies in the field of medicine, application of mAbs in the treatment of several disease conditions has been at the forefront [3].

Conclusion: Monoclonal antibodies (mAbs) have been applied in the treatment of non-infectious diseases such as cancer, immune diseases, arthritis and disorders resulting from organ transplantation. This review highlights mAbs applications in biomedicine, and discusses the state-of-the-art technologies related to their potential uses.

Keywords: Monoclonal antibodies (mAbs), cancer, autoimmune diseases, arthritis, biosimilars

Introduction:

Monoclonal antibodies (mAbs) are antigen-recognizing glycoproteins that are made by identical immune cells, all of which are clones of a unique parent cell. Since 2014, FDA has approved at least five monoclonal antibodies per year, and this trend shows no signs of slowing. The increasing demand for monoclonal antibodies (mAbs) used for diagnostic and therapeutic applications has led to the development of large scale manufacturing processes, with improvements in production achieved through continuous optimization of the inherent systems [1]. The number of monoclonal antibodies (mAbs) that have already been approved for therapeutic applications and for use in clinical trials have significantly increased in the past few years. Since 1985, approximately 100 monoclonal antibodies (mAbs) have been designated as drugs; new approvals continue to accrue [2]. Available mAbs are directed against a large number of antigens and used for the treatment of immunologic diseases, reversal of drug effects, and cancer therapy [6]. These therapies encompass a number of indications such as autoimmune disorders, infectious diseases, and oncology, among others [2]

Invention

The invention of monoclonal antibody (mAb) technology provided scientists with a tool to pursue that dream. In 1975, researchers César Milstein and Georges Köhler, working at the Laboratory for Molecular Biology in England, developed a technique for creating cells that could pump out streams of identical antibodies.

mAbs-1Fig. 1. Progressive humanization of antibodies.

A schematic representation of the advancement from fully mouse antibodies, represented by red domains, to fully human antibodies, represented by blue domains.

mAbs-2Fig. 2. Timeline of major improvements in monoclonal antibody development.

Examples of Monoclonal Antibodies

There are four ways in which scientists prepare monoclonal antibodies. They are:

  1. Murine: Murine monoclonal antibodies consist of mouse proteins, and their names end with the suffix – omab. E.g. Tositumomab (Cancer)
  2. Chimeric: These are also a combination of part mouse and part human. Their names end with – ximab. E.g. Rituximab (Cancer)
  3. Humanised: Humanised monoclonal antibodies are made of parts of mouse proteins attached to human proteins. Their names end with -zumab. Eg. Trastuzumab (Cancer)
  4. Human: These are made purely from human beings, and their names end with the suffix -umab. Eg. Ipilimumab (Skin Cancer)

Biosimilar mAbs

These are biologic therapies that are highly similar to the reference product in clinical potency and toxicity but may have slight differences in components that do not appear to affect their clinical efficacy or toxicity [4]. Biosimilar mAbs are being developed as the patents expire on existing products. Examples include mAbs similar to infliximab and adalimumab, which target tumor necrosis factor (TNF).

Bispecific antibodies (BsAbs)

These are antibodies with two binding sites directed at two different antigens or two different epitopes on the same antigen. The clinical therapeutic effects of BsAbs are superior to those of monoclonal antibodies (MoAbs), with broad applications for tumor immunotherapy as well as for the treatment of other diseases. Recently, with progress in antibody or protein engineering and recombinant DNA technology, various platforms for generating different types of BsAbs based on novel strategies, for various uses, have been established.

The Future of Monoclonal Antibodies

It is difficult to predict what the future of antibody humanization will look like. Over time, the humanization process of mouse-derived antibodies has become much more sophisticated, with several companies now performing in silico optimization of Complementarity-determining regions (CDRs)( they are part of the variable chains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively, where these molecules bind to their specific antigen) for T-cell epitope avoidance to reduce immunogenicity. Yeast display is a new technology that in theory avoids some of the disadvantages of the phage display process for monoclonal antibody generation. Newer transgenic mice that have a fuller complement of human antibody genes are also being used to develop a new generation of fully human monoclonal antibodies.

Conclusion

Monoclonal antibodies have also been applied in the treatment of non-infectious diseases such as cancer, immune diseases, arthritis and other disorders resulting from organ transplantation. This review highlights mAbs applications in biomedicine, and discusses state-of-the-art technologies related to their potential uses. With the advent of fully human MAbs, the efficacy and safety have improved in the treatment of various cardiovascular, cancer, respiratory, hematology, autoimmune diseases and infections. The introduction of biosimilars will increase the affordability and utilization of MAbs in the treatment of various diseases. Have the magic bullets arrived? We can now answer this question with a resounding yes. Mabs have made and are making major contributions to the therapy of human malignancies, and as new targets and pathways of human disease are identified, the role of Mabs for treatment of human disease will only continue to grow and expand.

Remarks: This article will be continuing with each individual Drug in detail as a series.

References

  1. Ribatti D. From the discovery of monoclonal antibodies to their therapeutic application: An historical reappraisal, Immunol Letters 2014; 161(1): 96-9.
  2. John P Manis, MD. Overview of therapeutic monoclonal antibodies: Jun 2022
  3. Wang S. Advances in the production of human monoclonal antibodies. Antibo Techn Journ. 2011;1:1-4
  4. Macdonald JC, Hartman H, Jacobs IA. Regulatory considerations in oncologic biosimilar drug development. MAbs 2015;7:653.
  5. Newsome BW, Ernstoff MS. The clinical pharmacology of therapeutic monoclonal antibodies in the treatment of malignancy; have the magic bullets arrived? Br J Clin Pharmacol. 2008;66(1):6-19.
  6. Geoffrey Banks, Monoclonal Antibodies: Past, Present and Future: January 23, 2018, https://www.nuventra.com/resources/blog
D.-Suryaprabha

D. Suryaprabha

Senior Executive-Clinical Research

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