Cancer, monoclonal antibodies

Noguchi, A., Takahashi, T., Yamaguchi, T., Kitamura, K., Takakura, Y., Hashida, M., and Sezaki, H. (1992) Preparation and properties of the immunoconjugate composed of anti-human colon cancer monoclonal antibody and mitomycin C—Dextran conjugate. Bioconjugate Chem. 3, 132-137. 

Thus far, Lhe discussion relaling to the medical uses of monoclonals has focused exclusively upon cancer. Monoclonal antibodies (and their derivatives), however, have a far broader potential therapeutic application. Actual/potential additional uses include detection and treatment of cardiovascular disease, infectious agents, and various additional medical conditions (Table 13.2). 

Iannello A, Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev. 2005 24 487M-99. 

Noguchi A, Takahashi T, Yamaguchi T, Kitamura K, Takakura Y, Hashida M, Sezaki H. P reparation and properties of the immuno-conjugate composed of anti-human colon cancer monoclonal-antibody and mitomycin C-dextran conjugate. Bioconj. Chem. 1992 3 132-137. 

Whereas epidermal growth factor (EGF) enhances the radiosensitivity of human squamous ceU carcinoma cells in vitro (197), addition of EGF to hormone-deprived MCE-7 breast cancer cells prior to irradiation results ia iacreased radioresistance (198). An anti-EGE-receptor monoclonal antibody blocks the abiUty of EGE to enhance growth and radioresistance. Tumor cells, the growth of which is stimulated by EGE, appear to be protected those where growth is iohibited are sensitized (198). 

Mammalian Cells Unlike microbial cells, mammalian cells do not continue to reproduce forever. Cancerous cells have lost this natural timing that leads to death after a few dozen generations and continue to multiply indefinitely. Hybridoma cells from the fusion of two mammalian lymphoid cells, one cancerous and the other normal, are important for mammalian cell culture. They produce monoclonal antibodies for research, for affinity methods for biological separations, and for analyses used in the diagnosis and treatment of some diseases. However, the frequency of fusion is low. If the unfused cells are not killed, the myelomas 1 overgrow the hybrid cells. The myelomas can be isolated when there is a defect in their production of enzymes involved in nucleotide synthesis. Mammahan cells can produce the necessary enzymes and thus so can the fused cells. When the cells are placed in a medium in which the enzymes are necessaiy for survival, the myelomas will not survive. The unfused normal cells will die because of their limited life span. Thus, after a period of time, the hybridomas will be the only cells left ahve. 

Recombinant humanized monoclonal antibodies have been used recently to target antigens that are preferentially located on cancer cells. Examples include trastuzumab and rituximab which are used to treat HER2 positive breast cancer and B-cell type lymphomas, respectively. Unwanted side effects include anaphylactic reactions. 

Bevacizumab (Avastin) Monoclonal antibody against ligand VEGFR Cancer Clinic... 

Targeted Cancer Therapy. Table 2 Main differences between monoclonal antibodies and small-molecule tyrosine kinase inhibitors... 

K., Abe, O., and Saito, K. (1987). Antitumor effect of adria-mycin entrapped in liposomes conjugated with anti-human alfa-fetoprotein monoclonal antibody, Cancer Res., 47, 4471-4477. 

Baldwin R.W. (1985) Monoclonal antibody targeting of anti-cancer agents. EurJ Cancer Clin Oncol, 21, 1281-1285. 

Figure 20. Selective cell targeting via specific monoclonal antibodies and/or antibody fragments directed against cancer cells and linked to the free amino groups of L-cysteine-coated metallic-core magnetic nanoparticles (MNP) (MNP = Co, Fe/Co, size 8-10 nm).

The cell surface contains antigens, which are referred to as CD, which stands for cluster of differentiation. The antibodies are produced against a specific antigen. When administered, usually by an intravenous injection, the antibody binds to the antigen, which may trigger the immune system to result in cell death through complement-mediated cellular toxicity, or the antigen-antibody cell complex may be internalized to the cancer cell, which results in cell death. Monoclonal antibodies also may carry radioactivity, sometimes referred to as hot antibodies, and may be referred to as radioimmunotherapy, so the radioactivity is delivered to the cancer cell. Antibodies that contain no radioactivity are referred to as cold antibodies. 

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