In vivo screening

 

In order to conduct a proof-of-concept study to evaluate the potential of an anticancer therapy, it is critical that the compound be well administered to animals. The required process is based on the following:

Preclinical formulation

The compound should be well-formulated and stable in solution for experimental use. Our laboratory is fully dedicated to the determination and preparation of the preclinical formulation of compounds and standard-of-care agents, as well as the testing of compound stability in solution. This restricted area ensures secured storage and safe preparation/handling of compounds.

Dose determination

In order to evaluate the antitumor activity of the compound, we need to determine the tolerated concentrations that will be injected in tumor-bearing animals. The tolerated dose determination is performed with a reduced number of healthy or tumor-bearing rodents. Other toxicity parameters that may be studied include hematological, blood biochemistry or histological analyses.

Route & schedule of administration

The study of compound half-life will enable us to choose the most appropriate route and schedule of administration for in vivo evaluation. In our analytical laboratory we develop, transfer and validate HPLC, HPLC/MS-MS and ELISA analytical methods for compound quantification in any biological matrix. PK and biodistribution studies could also be performed using radiolabelled compounds, AAS, ICPMS or µPET and lead to PK/PD modelling.

Antitumor activity

We can then evaluate the potential activity of the compound in a basic subcutaneous mouse tumor model, chosen based on target expression or results obtained during the cellular screening.
We have a panel of more than 100 subcutaneous tumor models of human or rodent origin. For the majority of these models we have tested standard-of-care agents and have defined a positive control that enables us to guarantee the reproducibility of the model. All the protocols involving animals adhere to European guidelines and are submitted to an external ethical committee. Oncodesign could enforce stricter animal welfare criteria if so desired by the client.

This in vivo screening approach is used to select lead compounds.