29.07.2021 duration: 3 min

Monoclonal antibodies & Ethical issues

Monoclonal antibodies are currently used for an ever increasing number of diagnostic and therapeutic applications. Typically, the expression of antibodies involves the use of mammalian cells, which in itself leads to ethical issues.

The following article examines the advantages and disadvantages of monoclonal as well as recombinant antibodies. It also highlights the necessity of tests and trials and why these can be viewed as ethically problematic.  

What is a monoclonal antibody?

A monoclonal antibody (in short: mAb or moAb) is an increasingly popular and important tool in the fields of biochemistry and medicine. It is made by cloning a white blood cell, which is always unique.

All subsequent antibodies derived this way trace back to this unique parent cell, while polyclonal antibodies are usually derived from several different plasma cell lineages.

As the name suggests – and opposed to polyclonal antibodies – monoclonal antibodies have a so-called monovalent affinity. In other words, they are only binding to the same epitope (the part of an antigen that is recognized by the antibody).

Advantages of monoclonal antibodies

While monoclonal antibodies only bind to one epitope, it is possible to enhance them by means of artificial engineering. By employing various techniques, labs can produce monoclonal antibodies that bind to a specific substance in order to detect or purify it. 

These capabilities are just two of the benefits of monoclonal antibodies that add to their popularity in molecular biology, biochemistry and medicine.

The most important advantages of mAbs are:

  • Homogeneity and consistency
  • Potential for renewability once a suitable hybridoma has been developed
  • Higher level of purity and concentration than polyclonal antibodies
  • Sensitivity with regards to the smallest changes in salt concentration and pH

Disadvantages of monoclonal antibodies

Under certain circumstances, the advantages of monoclonal antibodies that have been mentioned above can also be seen as disadvantages. Like two sides of a medal, certain strengths can turn into weaknesses, depending on requirements and point of view.

For one, the specificity of monoclonal antibodies naturally limits their scope of application. Due to their sensitivity, they are furthermore easily affected in terms of their functionality.

Other disadvantages may be that:

  • they are not suitable for use in assays such as hemagglutination involving antigen cross-linking
  • slight modifications affect the binding site of the antibody

Ethical issues of monoclonal antibodies

Some people object to drug trials involving humans as they see an ethical issue in the potential risks, even though all subjects taking part in trials do so voluntarily, and they often get paid for their participation.

Besides general questions of morals and religion, discussions about ethical issues in the pharmaceutical industry often revolve around animal rights.

Naturally, this is no different when discussing monoclonal antibodies whose origins can be traced to CHO or mouse cells. The use of animals – either as testing subjects or for production purposes – can be deemed unethical by some people.

What are recombinant antibodies used for?

However, animal cell culture technology has advanced significantly over the last few decades. There are strict guidelines in place to regulate the use of animals where it is still necessary.​1​

Additionally, if various scientific publications/articles​2​ are to be believed, the use of animals for the expression of antigen-specific antibodies is on the decline. This is owed to the fact that recombinant antibodies, derived from synthetic genes, are on the rise. 

Interested in recombinant antibodies?

    How recombinant antibodies overcome ethical issues

    But what exactly are recombinant antibodies? Recombinant antibodies are monoclonal antibodies that are generated in vitro using synthetic genes.

    While monoclonal antibodies are derived from CHO cells and other mammalian cell culture, no hamster, mouse or other animal is used, let alone harmed, in the process of recombinant antibody expression. 

    Apart from being ethically sourced, recombinant antibodies offer versatility as another major advantage. The most commonly used recombinant antibodies are scFv, Fab fragments and bispecific antibodies, the latter of which are more varied than monoclonal antibodies as they increase the therapeutic targets of one monoclonal antibody to two epitopes.

    1. 1.
      Gray AC, Bradbury ARM, Knappik A, Plückthun A, Borrebaeck CAK, Dübel S. Animal-derived-antibody generation faces strict reform in accordance with European Union policy on animal use. Nature Methods. Published July 27, 2020. Accessed July 28, 2021. https://www.nature.com/articles/s41592-020-0906-9
    2. 2.
      Rita Costa A, Elisa Rodrigues M, Henriques M, Azeredo J, Oliveira R. Guidelines to cell engineering for monoclonal antibody production. European Journal of Pharmaceutics and Biopharmaceutics. Published online February 2010:127-138. doi:10.1016/j.ejpb.2009.10.002
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