Quality Assistance - Development and validation of an antibody-drug conjugate bioassay

Antibody-drug conjugates (ADCs) are a class of drugs used in the treatment of different cancers. Unlike chemotherapy, ADCs are designed to only target and kill tumour cells. Structurally, ADCs are complex molecules composed of an antibody linked to a cytotoxic compound through the use of a linker. ADCs therefore combine the targeting capacity of monoclonal antibodies and the capacity to destroy cancer cells of cytotoxic agents.

In this context, Quality Assistance has developed a cytotoxicity assay using trastuzumab emtansine (T-DM1). T-DM1 is an ADC that combines the humanised trastuzumab antibody (anti-HER-2) and the potent anti-microtubule agent DM1 (derivative of maytansine) using a highly stable linker. This ADC is used as treatment for patients diagnosed with a HER-2 positive breast cancer.

This study demonstrates the successful development and validation of this method. It also highlights the importance of the revelator agent choice. Agents measuring the metabolic activity of the cells are not always the best choice depending of the cell culture conditions. It is therefore more appropriate to use agents that directly measure the cytotoxicity based on exclusion dyes, DNA intercalant agents or change of the mitochondria membrane potential.

The method was finally validated according to USP 1033 guideline in terms of specificity, linearity, precision (repeatability and intermediate precision) and relative accuracy. Moreover, the method was demonstrated to be stability-indicating and therefore allows for the detection of degraded samples.

Fabian Vandermeers, R&D Technical Leader at Quality Assistance, guides you through this bioassay
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European leader in analytical sciences

Quality Assistance S.A. is a leading European Contract Research Organisation providing the pharmaceutical industry with all the analytical services required by EMA and FDA regulations for the development and marketing of innovative human medicinal products.

We assist our clients from candidate selection, through non-clinical and clinical studies, to marketing authorisation, using our state-of-the-art, product-dedicated expertise in analytical sciences.
For each customer and each project, we design customised solutions, define analytical protocols, develop and validate specific new analytical methods and perform characterisation, stability, pharmacokinetic, biomarker and immunogenicity studies as well as batch release testing, in order to evaluate the Quality, Safety and Efficacy of the given drugs.

Technoparc de Thudinie, 2
6536 Donstiennes
Belgium

www.quality-assistance.com

Видео Quality Assistance - Development and validation of an antibody-drug conjugate bioassay канала Quality Assistance