Monoclonal antibodies toxicity

The cell surface contains antigens, which are referred to as CD, which stands for cluster of differentiation. The antibodies are produced against a specific antigen. When administered, usually by an intravenous injection, the antibody binds to the antigen, which may trigger the immune system to result in cell death through complement-mediated cellular toxicity, or the antigen-antibody cell complex may be internalized to the cancer cell, which results in cell death. Monoclonal antibodies also may carry radioactivity, sometimes referred to as hot antibodies, and may be referred to as radioimmunotherapy, so the radioactivity is delivered to the cancer cell. Antibodies that contain no radioactivity are referred to as cold antibodies. 

Panitumumab is a human monoclonal antibody directed against epidermal growth factor receptor. Common adverse events include dermatologic toxicities, fatigue, abdominal pain, nausea, and diarrhea. 

Preclinical studies should address the potential toxicity due to inappropriate release of the conjugated toxin. Preclinical toxicology of monoclonal antibodies may not require extensive animal studies but should be examined for cross-reactivity with antigenic epitopes present on normal cells in vitro and for the presence of human or rodent vimses. Early clinical trial should involve biodistribution studies with radiolabelled material. 

This approach appears somewhat irrational and without much scientific merit, since many of these new molecules are minimally toxic or nontoxic by this sort of acute evaluation. As in the case of interferons or monoclonal antibodies, the toxic effects observed in humans might not be predicted from safety assessments in rodents. An appropriate test species should be selected. Is the rat or mouse the appropriate species to evaluate a species-specific rDNA protein such as human growth hormone or interferons, or would nonhuman primates be more suitable Does the nonhuman primate really offer any advantages There is some consensus that the nonhuman primate may be a more appropriate species for testing some rDNA human proteins. 

Is the discovery and development of another blockbuster monoclonal antibody like rituximab a feasible research and development model today Many of the special events that contributed to its success are probably not replicable. As with several other successful drugs, the market turned out to be much larger than anticipated, so competition from other drugs being simultaneously developed was not so intense. Similarly, the ability to manufacture the drug in a cost-effective manner did not exist when the project was initiated, but there were other advantages unique to rituximab. Its toxicity is minimal, a... 

The conjugation of deacetylvinblastine to a monoclonal antibody that recognizes a tumor-associated antigen results in an agent with substantial antitumor activity in mice with relatively little toxicity (la). Conjugates of this type are of obvious interest for future clinical trials as site-directed cancer chemotherapeutic agents. 

Bispecific monoclonal antibodies (BsMAb) which combine the specificity of two different antibodies within one molecule and cross-link an effector cell or a toxic molecule with the target cell (Section 8.5.2). 

Another approach to selectively inducing tumour cell kilhng is by the use of bispecific monoclonal antibodies (BsMAb).They combine the specificity of two separate antibodies within one molecule and cross-hnk an effector killer cell or a toxic molecule with the target cell to be destroyed [75]. There are three major approaches for creating BsMAbs.They can be obtained by chemical cross-linking of two MAbs, by fusing two hybridomas [76], or by genetic... 

Studies in pre-clinical models with human tumours are often carried out in (immuno)defi-cient mice. However, particularly in the case of monoclonal antibody-directed therapy, it is important to recognize that these models, while useful, frequently over-predict activity and under-predict toxicity because the target antigen is tumour-specific in the animal but only tumour-associated in man. 

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