The importance of PK analysis

Following the initial in vitro screening of a new compound, it is essential to analyze how the body impacts the drug, following its administration. This is known as pharmacokinetics (PK), and it helps determining the absorption, distribution, metabolism, and elimination (ADME) of a drug. Since several factors can impact the PK of a drug, such as the body’s metabolism, it is essential to perform this assessment in a relevant animal model, which will generate predictive and translational data.

PK analysis is commonly performed by measuring the drug concentration in the blood/plasma or tissues at several timepoints after administration. PK analysis of a drug enables the calculation of key parameters, such as:

Cmax – peak concentration
Tmax – time to reach peak concentration
AUC – total drug exposure over time
t½ – half-life (time to reduce drug concentration by half)
CL – clearance rate
Vd – volume of distribution

The importance and contribution of biodistribution analysis

Analyzing the biodistribution of a drug is also very important, as it provides an insight to where the drug might accumulate. This information can provide you with a vast range of useful applications, such as assessing a patient’s response to treatment, identifying new biomarkers, or understanding the dynamics of specific cell subsets in the context of disease.

4 steps you need to follow for successful PK assessment of your compound

Relying on wild-type mice or inappropriate humanized models may result in a potentially viable drug candidate being rejected, or important adverse drug reactions not being detected, as occurred in the TeGenero 2006 clinical trial with TGN1412. This can happen when drug safety experiments are performed in PBMC-reconstituted mouse models that do not consider the contribution of myeloid cells to the elicited immune response and which contain a majority of pre-activated T cells.

We have developed a wide range of translational pre-clinical models to meet your research needs, which can be used alone or in complementary ways to maximize and accelerate your research. They are either readily available for purchase (see our Catalog Models) or can be developed specifically for you (see our Customized Models).

Our selection of catalog models includes different types of models useful for safety assessment.

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Humanized immune system (HIS) models

As part of our catalog, we also provide humanized mouse models with a human immune system (HIS), such as the genO-BRGSF-HIS and genO-BRGSF-A2-HIS models. These models are engrafted with human CD34+ hematopoietic stem cells, which provide a much more complete reconstitution of the immune system compared to human PBMCs, thereby making them more translational to clinical studies. Given their functional human myeloid and lymphoid compartments, permissiveness to PDX and CDX engraftments, and extended lifespan, these models are ideal for safety assessment of immunotherapies targeting myeloid and lymphoid cells, as shown in articles published by both Sensei Bio and genOway.

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Target-specific humanized models

A wide range of target-specific humanized strains is available and ready for purchase. These models are immunocompetent, and display a physiological expression of the human target. Some of the models present in our catalog include:

Several humanized immune checkpoint models, such as the genO-hCTLA-4 and the genO-hCD47/hSIRPα models, among many others. With these models you can assess the safety of your human-specific immunomodulators/immunotherapies. These models have proved successful in contributing to the safety testing of new therapies, as shown by Maxivax and Caedo Oncology.
Humanized CD3 and CD28 models are also available to help you assess the safety of new T-cell engagers, such as the genO-panhCD3 and genO-hCD28 models, as presented at the SITC 2022, and AACR 2024, respectively.
The humanized TFRC model (hCD71) allows you to test the safety of constructs aiming to cross the blood-brain barrier, or therapies targeting CD71-overexpressing cancers, as demonstrated by Bratti et al., 2024.
Our humanized FcγR model is a powerful tool for safety assessment of Fc-competent therapeutic antibodies.

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Cell lines

Another important consideration when performing safety tests for cancer drugs is whether the tumor might impact the drug’s pharmacokinetics or mechanism of action, and whether the activation status of the immune system could also impact the drug’s safety profile. Therefore, if you would like to analyze the safety of your drug in a cancer biology context, our humanized mouse models can be used for syngeneic studies, for which a complementary catalog of cell lines is available.

A variety of cell lines, such as colon carcinoma cells lines (MC38 and CT26, for C57BL/6 and BALB/c mice, respectively) or a lymphoma cell line (EL4), are available.
These cell lines are engineered to express human proteins such as CD19 or CD20 (in the EL4 background), or humanized immune checkpoints (in MC38 and CT26 backgrounds).
We also provide a range of reporter and Knockout cell lines, which can be used as a control for your efficacy studies and target validation.

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Immunodeficient models

In our vast portfolio, you can also find immunodeficient rodents. These models can additionally be used for safety assessment in very specific cases. These include analyzing potential on- and off-target effects of CAR-T therapies or testing the safety of gene therapy. Our immunodeficient models support PDX and CDX engraftment and can develop metastasis, as well as allow longer experimental timeframes due to their extended longevity.