Off-Target/On-Target Cytotoxicity Assay

This assay is designed to evaluate the selective cytotoxic effects of anticancer drug candidates by simultaneously assessing their therapeutic efficacy on a primary tumor target and their potential off-target toxicity on non-target organs—most notably, the liver.

Purpose of the Test

The MIVO multi-organ based assay integrates advanced three-dimensional tumor models with organ-specific tissues (e.g., hepatic tissues) within a unified, dynamic platform.

Its primary objective is to quantitatively assess tumor cell cytotoxicity (on target) while concurrently monitoring off-target toxicity in a secondary tissues. By mimicking the
physiological conditions of systemic drug circulation and fluidic connection of multiple organs, MIVO® platform provides a predictive measure of both on-target anticancer
activity and off-target toxicological responses, thereby informing optimal dosing strategies and enhancing drug safety profiles.

This assay serves as a pivotal component in the preclinical evaluation of novel therapies. Its novel and multiorgan design ensures the investigation of organ organ crosstalk and possible interplay during the drug treatment.

The MIVO® Advantage: A Superior Predictive Model

By incorporating a dynamic fluidic system, the assay overcomes the limitations of static models and single organ microphysiological systems. The continuous flow simulates physiological shear stress and circulation, ensuring realistic drug delivery, distribution, and inter-organ communication. This dynamic environment enhances the accuracy of predictive data on both on-target (tumor) and off-target (e.g., hepatic) cytotoxic effects, ultimately reflecting clinical scenarios more closely. (ref toxoefficacy)

Our Unique Value Proposition

Realistic 3D Tumor Microenvironment: The assay utilizes a three dimensional tissue models that preserve the complex cell-to-cell interactions and extracellular matrix characteristics found in vivo, enabling a more accurate prediction of therapeutic responses.
Dynamic Fluid Flow for Enhanced Drug Delivery and organ-organ connection: The MIVO multiorgan platform incorporates a fluid dynamic system that mimics systemic circulation and organ organ connection.
Quantitative Evaluation of Therapeutic Efficacy and Toxicity: The assay delivers robust, quantitative measurements of tumor viability reduction, thereby facilitating the optimization of dosing regimens and providing critical insights into the antitumor potential of new drug candidates.

Drug Efficacy Assay

In summary

Off-Target/On-Target Cytotoxicity Assay

READOUTS

  • Tumor cells viability
  • Tumor cells metabolism
  • Off-target toxicity (LDH)
live dead cells

Live & Dead assay is performed after exposure to test drug, to detect live and dead cells.

AlamarBlue s performed after exposure to different doses of test drug, as indirect measurement of cell viability Off-Target_On-Target Cytotoxicity Assay

AlamarBlue s performed after exposure to different doses of test drug, as indirect measurement of cell viability.

LDH activity is evaluated as a measure of off-target toxicity. Off-Target_On-Target Cytotoxicity Assay

LDH activity is evaluated as a measure of off-target toxicity.

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