Monoclonal antibodies predicting toxicity

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. 

Tissue Cross-Reactivity Studies for Monoclonal Antibodies Predictive Value and Use for Selection of Relevant Animal Species for Toxicity Testing... 

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. 

Revillard, J.P., Robinet, E., Goldman, M., Bain. H.. Latinne, D. and Chatenoud, L. (1995) In vitro correlates of the acute toxic syndrome induced by some monoclonal antibodies a rationale for the design of predictive tests. Toxicology, 96. 51-58. 

The other monoclonal antibodies shown in Table 17.2 produced either no toxicity or minimal biological effects in adult animals and no harmful effects to the fetus. One interesting observation is that even for those molecules that did show an effect in the fetuses, the effects that were observed were minor compared to effects that might be predicted based on observations in genetically deficient mice. Mice genetically altered to lack the a4 integrin are not... 

Monoclonal Antibodies An antibody is called monoclonal when each immunoglobulin is produced by a single clone of cells and hence is identical to every other molecule in the preparation, in terms of heavy as well as light chain structure. Thus they are highly specific and offer more consistent efficacy and predictable toxicity in vivo than the polyclonal counterparts. ... 

Based on the dramatic changes in volume of distribution and the free fraction of PCP found in serum, we predict that this form of therapy has the potential to rapidly reverse the toxicity of PCP, if sufficient Fab can be administered relative to the dose of PCP, The most practical method for making large quantities of antibodies with reproducible properties is through monoclonal... 

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