Cancer treatments monoclonal antibodies

Table 12.3 Approved unconjugated therapeutic monoclonal antibodies for treatment of cancer. ...

Hekman, A., Honselaar, A., Vuist, W. M., Sein, J. J., Rodenhuis, S., ten Bokkel Huinink, W. W., Somers, R., Rumke, P., and Melief, C.J. (1991). Initial experience with treatment of human B cell lymphoma with anti-CD19 monoclonal antibody. Cancer Immunol. Immunother. 32, 364-372. 

Avis, I. L., Kovacs, T. O., Kasprzyk, P. G., Treston, A. M., Bartholomew, R., Walsh, J. H., Cuttitta F. and Mulshine, J. L. (1991). PreeUnical evaluation of an anti-autocrine growth factor monoclonal antibody for treatment of patients with smaU-cell lung cancer. J. Natl. Cancer Inst. 83, 1470-1476. 

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. 

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). 

Umemura, S., Sekido, Y., Itoh, H., and Osamura, RY. 2002. Pathological evaluation of HER2 overexpression for the treatment of metastatic breast cancers by humanized anti-HER2 monoclonal antibody (trastuzumab). Acta Histochemica et Cytochemica, Kyoto 35(2), 77-81. 

Goldenberg, M.M., "Trastuzumab, a Recombinant DNA Derived Monoclonal Antibody, a Novel Agent for the Treatment of Metastatic Breast Cancer," Clin. Ther., 21, 309-318 (1999). 

The three monoclonal antibodies approved, noted in Table 23.1, in the last 7 years for treatment of patients with cancer include Alemtuzumab (Campath M) (Genzyme Corporation, Cambridge, MA, U.S.A.), Cetuzimab (Erbitux ) (ImClone Corporation, Branchburg, NJ, U.S.A.), and bevacizumab (Avastin ) (Genentech, South San Francisco, CA, U.S.A.). 

TABLE 4.3 Monoclonal Antibodies Approved for Cancer Treatment... 

Cetuximab (Erbitux) is a monoclonal antibody against the epidermal growth factor receptor, EGFR. It is approved for treatment of colorectal cancer. The development of Erbitux was much in the news in 2004 as a result of insider stock trading at ImClone in the face of an initial turndown by the FDA. The former head of ImClone, Sam Waksal, is spending a term of 7 years in jail for his role in the affair. Martha Stewart completed a jail term of several months in the same case. Erbitux was subsequently approved by the FDA on the basis of additional clinical information. 

Finally, bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody has also been approved for treatment of colorectal and breast cancer. There are several... 

The ground-breaking development of monoclonal antibodies by Kohler and Milstein [21] initiated the development of antibody-mediated therapeutics for cancer. Because of their unique specificity, MAb were predicted to become the magic bullets in the battle against cancer. Over the last two and a half decades MAbs have moved from clone to clinic for the treatment of various malignancies. Several MAbs are currently entering clinical trials and should appear on the market in the next few years. The first MAb for cancer therapy was approved in the US in 1997. 

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