Immunotoxicity evaluating

S6 [53], This document includes sections on immunogenicity as well as a brief section on immunotoxicity evaluation. Notably, the use of a standard tier approach was rejected in favor of case-by-case screening, followed by mechanistic studies as necessary. 

Luster, M.I. et al., Development of a testing battery to assess chemical-induced immunotoxicity National Toxicology Program s guidelines for immunotoxicity evaluation in mice, Fund. Appl. Toxicol., 10, 2, 1988. 

Biagini, R.E., Epidemiology studies in immunotoxicity evaluations, Toxicology, 129, 37, 1998. 

Hinton, D.M., US FDA Redbook II immunotoxicity testing guidelines and research in immunotoxicity evaluations of food chemicals and new food proteins, Toxicol. Pathol., 28, 467, 2000. 

Luster, M.L., Munson, A.E., Thomas, P.T., Holsapple, M.P., Fenters, J.D., White, K.L., Jr., Lauer, L.D., Germolec, D.R., Rosenthal, G.J. and Dean, J.H. (1988). Development of a testing battery to assess chemical-induced immunotoxicity National Toxicology Program s Guidelines for Immunotoxicity Evaluation in Mice. Fund. Appl. Toxicol. 10 2-19. 

Luster, M. I., A. E. Munson, P. T. Thomas, M. P. Holsapple, J. D. Fenters, K. L. White, L. E. Lauer, D. R. Germolec, G. J. Rosenthal, and J. H. Dean. Development of a testing battery to assess chemical-induced immunotoxicity National Toxicology Program s guidelines for immunotoxicity evaluation in mice. Fundam. Appl. Toxicol. 10 2-19, 1988. 

Immunotoxicity testing guidelines exist for small molecules where the toxicology is largely unpredictable and rodent species are typically used [4]. Despite the lack of a specific guidance on immunotoxicity evaluation until now, most biopharmaceuticals have assessed the immunotoxic potential of the biophar-maceutical as a part of general single- and/or repeat-dose toxicity studies [5,23]. 

The immunotoxicity evaluation follows a straightforward strategy which is detailed in Figures 3 and 4 below. 

CURRENT REGULATORY EXPECTATIONS EOR IMMUNOTOXICITY EVALUATION OE PHARMACEUTICALS... 

Finco-Kent D, Kawabata TT. Development and validation of a canine T-ceU-dependent antibody response model for immunotoxicity evaluation. J Immunotoxicol 2005 2 197-201. 

Gore ER, Gower J, Kurali E, Sui J-L, Bynum J, Ennulat D, Herzyk DJ. Primary antibody response to keyhole limpet hemocyanin in rat as a model for immunotoxicity evaluation. Toxicology 2004 197 23-35. 

The objective of this section is to provide a description of several immune parameters and methodologies that are used in the preclinical setting to characterize immune hazards for human risk assessments. The utility of a standalone functional evaluation, specifically the rat T cell-dependent antibody response (TDAR) model developed for regulated immunotoxicity evaluations (Gore et al, 2004), is mainly used for hazard identification, i.e., unintended immunosuppression. This assay is based on an end point parameter that is the... 

TABLE 5.1-2 Algorithm for Immunotoxicity Evaluation Using Host Resistance Assays Generalized Assay to Evaluate the Overall Health of the Immune System... 

There is an obvious need for running dedicated clinical immunotoxicity studies. Indeed, one of the major hmitations of current immunotoxicity evaluation is the lack of human data. Risk is therefore assessed largely on the basis of preclinical studies, but the suitability and predictability of animal findings is at best debatable. 

An important point to be considered when developing new biomarkers of immunotoxicity is the requirement for many of these to be applicable to animal studies, as well as clinical trials in order to improve the transition from preclinical to clinical immunotoxicity evaluation. In the long run, strategies for animal studies intended to predict unexpected immunotoxicity can be expected... 

---