The History and Rationale for Monoclonal Antibodies in the Treatment of Hematologic Malignancy

Author: Dillman R.O.

Source: Current Pharmaceutical Biotechnology, Volume 2, Number 4, December 2001 , pp. 293-300(7)

Publisher: Bentham Science Publishers

Abstract:

The potential of antibodies as “magic bullets” for cancer therapy has been appreciated for nearly a century. During the past 25 years, various scientific developments have made possible the production of unlimited quantities of clinical-grade murine, chimeric, and humanized monoclonal antibodies (MoAbs). Intact, unconjugated MoAbs may: [1] produce anticancer effects through the immune system on the basis of interactions between the Fc portion of antibody and complement proteins and / or effector cells [2] induce regulatory effects by neutralizing circulating ligands or blocking cell membrane receptors, thereby interfering with ligand / receptor interactions and signal transduction [3] serve as immunogens for anti-cancer vaccines through the anti-idiotype-network cascade. Conjugated MoAbs can serve as carriers of other agents such as radioisotopes, natural toxins, chemotherapy drugs, cytokines, and immune cells. Important aspects of the antigenic target are the degree to which it is tumor-specific or tumor-associated, whether it internalizes or not, whether it is shed, the density of expression, and the physiologic significance of the antigen to the target cell. The clinical foundation for antibody-mediated therapy was laid in the 1980s when investigators established the safety of antibody administration, defined certain predictable antibody-mediated toxicities, and confirmed that antibodies could reach tumor targets and produce antitumor effects. A major limitation of these early mouse monoclonal antibodies was overcome with the production of antibodies with varying degrees of humanization. In 1997 rituximab (Rituxan?), a mouse-human chimeric anti-CD20, became the first MoAb approved by regulatory agencies for the treatment of a human malignancy.

Keywords: Monoclonal Antibodies; magic bullets; chemotherapy drugs; Complement mediated cytotoxicity (CMC); Chemotherapy-Antibody Conjugates; IMMUNE EFFECTS; Human antichimera; Granulocyte-macrophage

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389201013378617

Publication date: 2001-12-01

• Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.

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