Human natural antibodies

TABLE II. HUMAN NATURAL ANTIBODIES AGAINST GLYCOLIPIDS HAVING TERMINAL N-ACETYLGALACTOSAMINE RESIDUES... 

Antibody-based immimotherapy is often limited by a weak immunogenetic response. The complexity associated with the development of humanized antibodies has hindered progress for immimosuppressive therapy. Recently the direct use of human natural antibodies such as anti-Gal for the specific deletion of targeted bacterial cells has become very attractive [139,140]. The feasibility of using antibody targeting... 

Oriol R, Ye Y, Koren E, Cooper DKC. Carbohydrate antigens of pig tissues reacting with human natural antibodies as potential targets for hyperacute vascular rejection in pig-to-man organ xenotransplantation. Transplantation 1993 56 1433-1442... 

Alving, C. R. (1984). Natural antibodies against phospholipids and liposomes in humans, Biochem. Soc. Trans.. 12. 342-344. 

Trastuzumab is a recombinant DNA-derived, humanized monoclonal antibody that binds to the extracellular domain of the human epidermal growth factor receptor HER-2/ . This antibody blocks the natural ligand from binding and down-regulates the receptor. Trastuzumab is approved for the treatment of metastatic breast cancer in patients whose tumors overexpress HER-2/ . As a single agent it induces remission in about 15-20% of patients in combination with chemotherapy, it increases response rate and duration as well as 1-year survival. Trastuzumab is under investigation for other tumors that express HER-2... 

Figure 1. Natural antibodies in normal human and rabbit sera against liposomes containing no glycolipid, galactosylceramide, or lactosylceramide. Glucose release measured from liposomes containing DMPC, CHOL, DCP, and, where indicated, galactosylceramide (150 fig/nmol PC) or lactosylceramide (150 ng/fimol PC).

TABLE I. HUMAN AND RABBIT NATURAL ANTIBODIES AGAINST DIGALACTOSYL DIGLYCERIDE AND CERAMIDE TRIHEXOSIDE... 

We have demonstrated that every one of the human and rabbit sera tested have natural antibodies against several glycolipids. Most of the glycolipids used as antigens in this study normally occur in human and rabbit tissues (18), and therefore many, if not all, of the activities described are due to autoantibodies. 

Cornelia, K., Nakamura, M., Melnik, K., Chosy, J., Zborowski, M., Cooper, M. A., et al. (2001) Effects of antibody concentration on the separation of human natural killer cells in a commercial immunomagnetic separation system. Cytometry 45, 285. 

Other species of hybridomas, including human, have been produced but are generally created by the use of viruses conferring cellular immortality. Artificial immunization of the donor is often not practical or ethical and so cell lines are often derived from peripheral lymphocytes obtained from individuals naturally immune to the target substance. Some human monoclonal antibody secreting cell lines have been derived from spontaneously occurring myelomas, but this line of approach frequently is unrewarding as the probability that the antibody will be one of interest is remote. 

Kasaian MT, Ikematsu H and Casali P, Identification and analysis of a novel human surface CD5-B lymphocyte subset producing natural antibodies, J. Immunol., 148 2690-2702, 1992. 

In addition to its analytical value, this phenomenon is probably the basis of the important mechanism by which humans develop natural immunity.7 In fact, it has also been postulated that exposure to these cross-reacting, T-cell-dependent organisms is the most satisfactory explanation for the eventual maturation of the polysaccharide immune-response in infants.185 It can be shown, for instance, that there is an age-related increase in natural antibodies to the group A meningococcal polysaccharide in children, even though the group A organism is... 

In the 1980s, monoclonal antibodies were hailed as magic bullet therapeutics for the treatment of cancer, autoimmune disorders, and infectious diseases. Humanized monoclonal antibodies (MAbs) are now succeeding as drugs where mouse MAbs failed. Fully humanized MAbs are in the development pipeline, and therapeutic-biospecific MAbs are extending the versatility of nature s magic bullets. Several MAbs are now FDA-approved drugs (Table 2). Several MAbs are also in development (Table 3).3... 

Alemtuzumab is a humanized monoclonal antibody directed at cells that express the CD52 surface antigen which is found on both T- and B -lymphocytes, as weU as macrophages, monocytes, and natural killer (NK) cells. When alemmzumab binds to the CD52 surface antigen, antibody-dependent lysis occurs, which removes T cells from the blood, bone marrow, and organs, resulting in T-ceU depletion. 

The first hurdle to xenotransplantation is hyperacute rejection (HAR), which can destroy a transplanted organ in minutes to a few horns [2]. HAR of a pig organ in humans is triggered by the binding of xenoreactive natural antibodies to the endothelial lining of the blood vessels within the graft. In 1992 Cooper and coworkers... 

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