Monoclonal antibodies and antibody-based entities are a major class of therapeutic proteins. The surge in development of monoclonal antibodies is predominantly due to the utilization of technologies for producing fully human antibodies, namely phage display and transgenic mice with human humoral immune systems. Human CD48, a cell-surface adhesion molecule, is a potential tumor target for the treatment of white blood cell malignancies, principally leukemia and lymphoma. A truncated, secreted form of CD48 was expressed in CHO cells, and was shown to bind to existing anti- CD48 murine antibodies. A human anti-CD48 scFv antibody fragment, (designated scFv-N2A) was previously isolated using phage display technology from a synthetic human scFv immunoglobulin gene library. The scFv-N2A was reassembled as a human IgG1 monoclonal antibody (designated IgG1-N2A), expressed in CHO cells and the binding of IgG1-N2A to recombinant CD48 was confirmed by enzyme-linked immunosorbent assay, surface plasmon resonance and fluorescence activated cell sorting. IgG1-N2A binding to CD48 on Raji cells showed that the specificity of the human antibody for GPI-linked CD48 was conserved. In biological studies using a human lymphoma cell line (Raji), it was found that the IgG1-N2A antibody was able to induce potent growth inhibition, with a 68% reduction in viable cells. Furthermore, Raji cells treated with IgG1-N2A showed evidence of increased ethidium bromide uptake and cell shrinkage, which are characteristics associated with direct induction of apoptosis. The data suggests the novel human anti-CD48 IgG1-N2A monoclonal antibody can block proliferation and promote apoptosis of lymphoma cells, and therefore has potential as a lead antibody candidate for the treatment of white blood cell malignancies.

Thesis (doctoral)--Lund University, 1998. / Thesis statement on t.p. verso. Includes bibliographical references.

Thesis (doctoral)--Lund University, 1998. / Thesis statement on t.p. verso. Includes bibliographical references.

Thesis (MSc (Veterinary Tropical Diseases, Veterinary Science))--University of Pretoria, 2008. / Includes bibliographical references. Also available in print format.