Joint abc biopply’s 3R initiative introducing two novel approaches to preclinically assess off-target ADC toxicity ex vivo
Determining off-target cytotoxicity is an essential step in drug development. Today, it still requires the intensive use of corresponding animal models, especially for the development of antibody-drug-conjugates (ADC). abc biopply now offers, as a further step of its 3R initiative and together with its partner ReachBio, two highly accurate and novel services to assess off-target cytotoxicity. All assays are ex vivo and can be performed on cells and organoids from a multitude of species.
Together, those assays provide a comprehensive data set to assess off-target cytotoxic effects of ADCs accurately and reliably while effectively minimizing animal testing.
Off-target cytotoxicity in the hematopoietic system ADCs combine the benefits of therapeutic antibodies with the effect of potent cytotoxic drugs. Such cytotoxins are attached to the antibodies via a specific linker. Hematopoietic off-target cytotoxicity occurs when the payload of the ADC is released through unwanted cleavage of the linker while the ADC is still in circulation. ReachBio has developed two novel cell-based assays (further information) that address this effect and accurately inform on potential off-target cytotoxicity on hematopoietic cells:
A specifically modified colony forming assay for the use of ADCs
A neutrophil differentiation assay that addresses linker stability
From: Off-Target Toxiciy and Linker Stablility, White Paper, Emer Clarke, ReachBio
Off-target cytotoxicity on epitope-expressing secondary antibody targets Therapeutic antibodies are ideally selected against epitopes predominantly expressed in diseased tissues (e.g. cancer). However, most target proteins are also found in several other organs as well. Consequently, these organs become a target of the ADC and may be affected by the cytotoxic payload. abc biopply has developed the 3D CoSeedis™ Off-Target Cytotoxicity in chip Assay to specifically address those effects in highly accurate and reliable 3D disease models of various organs. The physiological accuracy of 3D CoSeedis™-derived organoids combined with the statistical relevance of abc biopply’s in chip assays makes this assay an important ex vivo tool in the assessment of off-target cytotoxicity.
Together, those assays provide a comprehensive data set to assess off-target cytotoxic effects of ADCs accurately and reliably. Furthermore, they substantially help reducing animal testing.
Would you like to know more on our off-target toxicity services? Are you interested to get more information on abc biopply’s preclinical disease models? I am looking forward to answering your call.