Classic and evolving approaches to evaluating cross reactivity of mAb and mAb-like molecules – A survey of industry 2008–2019

MacLachlan, Timothy K.; Price, Shari A.; Cavagnaro, Joy A.; Andrews, Laura; Blanset, Diann; Cosenza, Mary Ellen; Dempster, Maggie; Galbreath, Elizabeth; Giusti, Anna Maria; Heinz-Taheny, Kathleen; Fleurance, Renaud; Sutter, Esther; Leach, Michael W.

doi:10.1016/j.yrtph.2021.104872

Cited by 7 publications

(1 citation statement)

References 13 publications

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“…There is an ongoing debate on the significance of TCR data for predicting the effects of antibodies in humans, because organs and tissues that are positive in TCR studies do not necessarily match the target organs of toxicity 3 , 10 , 11 . One reason for this discrepancy may be the difficulty in designing IHC assays that sufficiently achieve the objectives of TCR studies.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic antibodies: technical points to consider in tissue cross-reactivity studies

Fujii,

Kato

2024

J Toxicol Pathol

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Tissue cross-reactivity (TCR) studies for the development of therapeutic antibodies are conducted to estimate any possible binding sites within the human body that can be affected by the antibody when assessing safety in humans. Any possible binding sites include specific binding sites of the antibody to its target antigen and nonspecific or off-target binding sites. In TCR studies the therapeutic antibodies and immunohistochemistry (IHC) of frozen tissues must be applied in assays. However, there are technical issues with applying a therapeutic antibody or test article to IHC, such as human-on-human staining, difficulty in applying the test article to IHC, and retention of the target antigen in frozen sections. In the current review, we introduce three case studies in which these technical issues were addressed, and propose a practical scheme for points to consider when conducting a TCR study. Information on the target antigen distribution obtained through robust assays and case-by-case strategies were found to be useful for understanding and assessing the relevance of toxic effects between animals and humans. Thus, we anticipate that by considering the points discussed in the current review and combining the data with information on the biological features of the target antigens and therapeutic antibodies, it will be possible to predict safety risks in humans with higher accuracy.

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Section: Discussionmentioning

confidence: 99%