Lord Dowding Fund for humane research

 

National Antivisection Society

Artificial Lymph Node: Testing human specific immune reactions

21 April 2010

It has been stated that the “development of therapeutical [sic] monoclonal antibodies has resulted in an increased need for primates in reproductive toxicology since the immune system in macaques is much more similar to humans compared with rodents.”(1)

However, as seen in previous disastrous human drug trials such as TGN1412, the immune systems of non-human primates are not sufficiently similar to those of humans to detect human immune reactions. The importance of testing human immune reactions to many modern biopharmaceuticals has emerged due to the very high degree of species specificity of drugs.

1

The lymphatic system is involved in human immunity(2). Lymphatic fluid transports bacteria and other foreign agents along the lymph vessels to the lymph nodes. Lymphatic fluid is presented to antigens held in the nodes as it is filtered through them. As fewer vessels leave the node than enter, flow through the nodes is slow, allowing time for foreign agents to be destroyed by the antigens(3). Lymphocytes, found in the lymph node, are antigens which are primarily responsible for specific immunological responses(4).


As animals possess an often significantly different immune system, it is insufficient to carry out tests with any animal species to assess the efficacy and safety of drugs in humans. The creation of a fully human Artificial Lymph Node (ALN) circumvents “the limitations associated with the use of animal models”(5).


The ALN model uses a bioreactor which is able to control the environment of the tissues being grown. The model is also reproducible which is important for its possible role in drug development and screening. The ALN mimics the physiology of the lymph node in the human body by integrating mobile and immobile cell phases to ensure the cells interact effectively(6).


A perfusion of cells and media flow from an outer culture space into a central culture space, which is a fixed matrix containing immobile cells. This allows cells flowing through the system to be presented to the fixed cells. This emulates the actions which occur in the lymph node when the lymphatic fluid flows into the node, passing by the lymphocytes which carry out an immune response. As this system creates an environment which is similar to that of the lymph node, it will be useful for looking at the effects of drugs and cell therapies(7).


Dr. Uwe Marx, one of the key scientists in the development of the ALN model, purports that in order to develop and adopt such models across the EU, a “human in vitro organ” program should be designed, specifically “for predictive reliable substance testing” incorporating disciplines such as tissue engineering, bioreactors, and computational models(8).

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1. http://ec.europa.eu/health/ph_risk/committees/04_scher/docs/scher_o_110.pdf
2. http://uhaweb.hartford.edu/BUGL/immune.htm#top
3. Marieb, E.N (1992) Human Anatomy and Physiology 2nd Edition, The Benjamin/Cummings Publishing Company, Inc. California
4. Miller, J.F.A.P, Lymphocytes, In: Dulbecco, R (Ed) (1991) Encyclopedia of Human Biology, Vol. V, Go-Me, Academic Press, Inc USA
5. http://www.probiogen.net/english/news/view_newsfile.php?id=134
6. Pörtner, R and Giese, C, An Overview on Bioreactor Design, Prototyping and Process Control for Reproducible Three-Dimensional Tissue Culture. In Marx, U and Sandig, S (2007) Drug Testing In Vitro: Breakthroughs and Trends in Cell Culture Technology, WILEY-VCH, Germany
7. Hitchcock, T and Niklason, L (2008) Lymphatic Tissue Engineering Progress and Prospects, Annals of the New York Academy of Science Vol. 1131, pp: 44-49
8. Pers. Comm. Dr Uwe Marx 14/04/08

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