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recombinant antibodies and cancerAntibodies and cancer
Cancer and its treatment are not normally associated with autoimmune diseases. But the use of plant-derived antibodies to target tumour cells through immune-mediated killing involves the destruction of body cells by its own immune system. Therefore, the use of antibodies in cancer treatment shares many traits with autoimmune diseases, despite their overall difference. This section is included as an example in which immune molecules are used to augment the immune system, rather than to inhibit it, and elicit a beneficial immune response against the body's own cells. Anti-human epidermal growth factor receptor-2 antibodies in breast cancer treatment and GA733-2 antigen used in colorectal cancer treatment will be used to discuss the current status of research on antibody-based cancer treatments.
According to the World Health Organization (WHO), breast cancer is one of the most common cancers in women. One cell surface protein that is upregulated in breast cancer cells is the human epidermal growth factor receptor-2 (HER-2). Her-2 is a transmembrane tyrosine kinase that activates downstream signalling cascades through its phosphorylation activity. Galeffi et al. have successfully expressed a single-chain antibody (fragment) against HER-2 in transgenic tobacco plants. scFv- αHER2 appears to be an intrinsically stable scFv molecule, accumulates in the plant cell cytosol and maintains its functionality. Their results also suggest that plant-derived anti-Her-2 antibodies bind to human breast cancer cells with specificity, which make them a strong candidate for anti-cancer drugs.
Colorectal cancer is one of the top five cancers in the world. As such, research on potential anti-colorectal cancer treatments represents an important area within the sciences. In colorectal cancer, there are several cell surface proteins that are upregulated and are good potential cancer-specific targets. These include c-erbB2, EGF-receptor, CEA, and GA733-2. Of these, GA733-2 is a cell surface protein involved in cell adhesion[4,5].
Verch et al. used plant-derived and animal-derived GAD to immunize mice against these antigens, which are present on the surface of colorectal cancer cells. They found that the expression of GAD733-2 in plant cells was slightly higher than that in animal cells. Furthermore, cytotoxic killing observed in cancer cells was effective with both plant-derived GAD733 antigen and cell-derived GAD733 antigen, which has thus far been the standard. The results obtained by Verch et al. suggest that plant-derived anti-colorectal antigens are just as specific and effective as those produced in animal cells and are therefore a promising alternative in the treatment of colorectal cancer.
Cancer treatment through targeting by cancer-specific antibodies or antigens is a relatively new and novel approach. With regard to breast cancer and colorectal cancer treatment, the use of transgenic plant production systems seems to be highly suited to this endeavor. The reactivity and specificity of plant-derived immune proteins matches that of other production systems currently used and has the further advantage of being easily scaled-up for mass production and does not transmit many of the pathogens that other production systems do. The next step in the development of plant-based anti-cancer antigens and antibodies is to verify the results observed in mice in humans, to improve both the protein yield and confirm the safety of this approach.
references1) World Health Organization. Cancer. http://www.who.int/cancer/en/. Accessed Mar 29, 2006.
2) Galeffi P, Lombardi A, Donato MD, Latini A, Sperandei M, Cantale C, Giacomini P. Expression of single-chain antibodies in transgenic plants. Vaccines 2005, 23: 1823-7.
3) Emens LA. Trastuzumab: Targeted therapy for the management of HER-2/neu-overexpressing metastatic breast cancer. American Journal of Therapeutics 2005, 12: 243-53.
4) Verch T, Hooper DC, Kiyatkin A Steplewski Z, Koprowski H. Immunization with a plant-produced colorectal cancer antigen. Cancer Immunol Immunother 2004, 53: 92-99.
5) Vaquero C, Sack M, Schuster F, Finnern R, Drossard J, Schumann D, Reimann A, Fischer R. A carcinoembryonic antigen-specific diabody produced in tobacco.