Drug discovery and development is a complex process that involves identifying potential drug candidates, testing them in vitro and in vivo, and finally obtaining regulatory approval for clinical use. The process is time-consuming, expensive, and often fails due to poor efficacy or toxicity. One of the main challenges with the drug discovery paradigm has always been the poor translational gap between inexpensive in vitro studies and significantly costly in vivo studies. Traditionally, cell culture models have been inadequate in recapitulating the complex in vivo microenvironment and thus have been limited in their ability to predict in vivo efficacy and toxicity. While no model is perfect, in vivo animal studies do not well-translate to results obtained in human clinical trials, particularly with regard to toxicology.
In Vitro Antibody Pharmacokinetics Assay
One of the services we offer is our In Vitro Antibody Pharmacokinetics Assay, which measures the distribution of biologicals, including antibody drugs, into solid tumor models. The assay utilizes tumor spheroid models and high content confocal imaging to assess the distance and quantity of antibody penetration into tumor spheroids. The assay can screen the relative differences in distribution of various biologicals, including antibody drug conjugates, antibody fragments, alternate domain antibodies, affibodies, and nanobodies. The assay can measure distribution curves, velocity curves, TD50 values, and concentration-time curves. The assay offers a cost-effective and time-saving alternative to animal studies for drug development.
3D Cell Culture Models
In vitro models are useful in drug development because they can provide a cost-effective way to screen potential drug candidates before moving on to more expensive and time-consuming in vivo studies. However, traditional 2D cell culture models have limitations in replicating the complex in vivo microenvironment, which is where 3D cell culture models come in. 3D cell culture models better mimic the in vivo microenvironment and can offer improved in vivo relevancy, allowing for more accurate predictions of in vivo efficacy and toxicity. Additionally, 3D cell culture models can be used to confirm results of in vitro screening using 2D cells and for screening hits and lead compounds for potential toxic liabilities.
Overcoming Challenges
Assessing the distribution of biologicals for drug development is a costly and time-consuming process that typically requires the use of animal studies. Heterogeneous distribution of biologicals (especially antibody drugs) in tumor tissue has been recognized as a major issue for immunotherapy. Transport of biologicals into tissues is a complex process involving a combination of factors. The main mechanism by which biologicals distribute throughout tissue is convective transport. However, in solid tumors, functional lymphatic vessels are rare, leading to an increase in hydrostatic pressure, reducing the propensity of the convection gradient to drive macromolecules into the tumor. After permeation into the tissue compartments, distribution relies on a balance of diffusion, convection, and affinity to target antigens within the interstices and cell surfaces.
Our In Vitro Antibody Pharmacokinetics Assay overcomes these challenges by utilizing tumor spheroid models, grown to approximately 200 μm in diameter, and treating them with antibody therapeutics at various concentrations. The tumor spheroids are then fixed at specified time points, labeled with fluorescent secondary to label therapeutic antibody, and subjected to tissue clearing to render them transparent. High content confocal imaging is used to analyze the resultant images and assess the distance and quantity of Ab penetration into tumor spheroids. The assay can measure distribution curves, velocity curves, TD50 values, and concentration-time curves.
Data is analyzed using high content screening and markers such as DAPI. The assay can measure distribution curves, velocity curves, TD50 values, and concentration-time curves. The analysis involves assessing the distance and quantity of antibody penetration into tumor spheroids using confocal imaging.
This In Vitro Antibody Pharmacokinetics Assay offers a cost-effective and time-efficient alternative to animal studies for drug development. The assay can screen the relative differences in distribution of various biologicals, including antibody drug conjugates, antibody fragments, alternate domain antibodies, affibodies, and nanobodies. The assay can measure distribution curves, velocity curves, TD50 values, and concentration-time curves. The assay offers a cost-effective and time-saving alternative to animal studies for drug development. By utilizing 3D cell culture models and high content confocal imaging, the assay can provide more accurate predictions of in vivo efficacy and toxicity. To learn more about this assay, please reach out to a member of our team to get started today!