Potential for recombinant immunoglobulin constructs in the management of carcinoma

Numerous monoclonal antibodies (MoAb) have been developed and currently are being evaluated in both diagnostic and therapeutic clinical trials. Despite the major advances fostered by MoAb technology, several limitations inherent to the use of MoAb exist. For example, MoAb may not have the desired plasma pharmacokinetics and metabolic properties, and they may be immunogenic, thus reducing the possibility of numerous administrations.

Recombinant DNA technology is used to develop (1) mouse-human chimeric antibodies in which the constant region of a murine antibody is replaced with the human constant region, (2) chimeric antibodies with domain-deletions or alterations in glycosylation, and (3) sFv molecules, i.e., recombinant proteins composed of a VL amino acid sequence of an immunoglobulin tethered to a VH sequence by a designed peptide.

This article reviews some of the genetic modifications that can be made with recombinant or chimeric immunoglobulin forms; two anti-TAG-72 MoAb, B72.3 and CC49, are used as examples. The immunoglobulin molecules that have been generated include those with alterations of subclass, domain deletions, and glycosylation, as well as those sFv molecules that have been prepared. The immunochemical and biologic properties of these novel immunoglobulin forms are described.

Recombinant DNA technology makes feasible the development of novel immunoglobulin forms. These genetic modifications may result in more useful diagnostic reagents and in the production of more stable immunoconjugates with the characteristics of more efficient tumor cell killing.