History

Currently, dynamic changes are taking place in the field of oncology. Remarkable advances have been made in elucidating the complex mechanisms of cellular signaling and malignant transformation, providing unique targets for therapy. Monoclonal antibodies (MoAbs) represent a subset of these newer, targeted therapies. MoAbs are designed to target specific surface proteins found on tumor cells, thus selecting malignant cellular clones for destruction while sparing healthy cells. This streamlined approach offers significant advantages over traditional chemotherapy, where healthy cells are often sacrificed in order to eradicate malignant cells. Recent improvements in technology and laboratory methods have enhanced the effectiveness of MoAbs, making them more amenable to clinical use.

Interestingly, while most of the currently available MoAbs have entered the marketplace in the past decade, the notion of antibody therapy has been around for years. Conceptually dating back to the nineteenth century, the initial idea of "serotherapy" was developed by Behring through his work with tetanus toxin. He discovered that immunizing toxin-naive animals with serum from animals exposed to tetanus toxin provided a protective effect against lethal doses of tetanus. Thus, he concluded that some form of antitoxin develops upon exposure to lower doses of toxin, providing future protection against the disease.1 Rapidly building on this concept of a "magic bullet," Hericourt and Richet prepared an "antiserum" to extracts of osteogenic sarcoma, which they used to treat patients with the disease. In 1953, Pressman and Korngold showed that antibodies could specifically target tumor cells, thus renewing interest in using immunotherapy for the treatment of cancer.2 Another breakthrough occurred in 1968, when Porter and Edelman identified the "antitoxin," or Y-shaped immunoglobulin structure well-known today.3 Finally, in 1975, the Nobel prize-winning publication by Kohler and Milstein described a realistic methodology for the creation of compounds that specifically select and bind to cancer cells. Their "hybridoma" cell lines were created from animals repeatedly immunized with target antigen. Subsequently, the B lymphocytes of these animals were isolated and immortalized, and the ability to produce specifically targeted antibodies was retained.4 Thus began the serious evaluation of MoAbs as potential therapeutic agents in the treatment of cancer.

Three types of MoAbs have emerged, representing three distinct therapeutic strategies: unconjugated MoAbs, immunotoxin-conjugated MoAbs, and radionu-clide-conjugated MoAbs.1 The unconjugated MoAbs represent the simplest form of therapy, where the antibody itself achieves cell death through stimulation of host immune effector mechanisms. The conjugated MoAbs, on the other hand, are covalently linked to either a toxin or a radioisotope. The release of the toxin/ radioisotope upon direct delivery to the targeted cell accounts for the cytotoxicity of these compounds.5

0 0

Post a comment