Melvyn Little

Of mice and men: hybridoma and recombinant antibodies

Thousands of mouse monoclonal antibodies have been produced from hybridomas over the past 25 years. The same technique can now be used to clone human antibodies from transgenic mice. Full-length antibodies and recombinant fragments engineered for various diagnostic and therapeutic applications can be obtained in reasonably large amounts after expression in mammalian cells, milk and plants.

Recombinant chimeric OKT3/IgM antibodies for immune suppression: evaluation in a human CD3 transgenic mouse model.

ScOKT3-gammaDeltaIgM VAEVD is a recombinant chimeric anti-CD3 antibody variant consisting of the light and heavy variable binding domains of the OKT3 monoclonal antibody and the CH3 and CH4 domains of a human IgM mutation linked by a human IgG3 hinge region. Due to the IgM Fc domains, scOKT3-gammaDeltaIgM VAEVD antibodies are able to form polymeric structures. Independent of their polymerization state, they possess in vitro CD3 modulating and immunosuppressive properties while inducing only minimal T cell activation compared to their monoclonal counterpart. To evaluate the in vivo efficacy of the antibodies, an adjuvant-induced chronic inflammation was established in human CD3 transgenic mice. Administration of four doses of 15 microg of isolated scOKT3-gammaDeltaIgM VAEVD monomers and pentamers significantly reduced diameters of inflamed ankle joints in a manner comparable to the monoclonal antibody OKT3. Additionally, the antibody treatment lead to a significant reduction of the cytokine levels (IL-2, TNF-alpha and INF-gamma) in the mices sera. These results suggest that scOKT3-gammaDeltaIgM VAEVD antibodies may provide a useful alternative to the OKT3 mAb for clinical immunosuppressive treatment for auto-aggressive diseases or for organ-transplantation.