2D vs 3D
Traditional two-dimensional (2D) cell culturing techniques have been accepted as economical and convenient in vitro analysing strategies to assess the characteristics of antibody-drug conjugates (ADCs) and other therapeutic agents. With the methodology established over a century ago, traditional techniques grow cells in two dimensions, by attaching cells on a plastic substrate or suspending cells in a thin layer of liquid medium, resulting in monolayer cell cultures. Those monolayer cells are simple and ready-to-use models for the high throughput screening of newly developed ADCs. In vitro analysis using 2D cell culture models provides primary indications of the targeting ability, internalization efficiency, and cytotoxicity of ADCs. However, failures of 2D-model-screened drugs in pre-clinical in vivo tests or clinical trials indicate that in vitro 2D cell cultures are not necessarily adequate models to precisely reveal the in vivo behaviours and dynamics of drugs.
For the development of highly efficient therapeutic agents, anti-cancer ADCs as examples, the targeting ability, internalization efficiency, drug releasing capacity and payload cytotoxicity of ADCs, as well as their tissue penetration ability, distribution pattern and bystander killing efficiency should all be assessed and optimized. However, in traditional 2D models with only a single layer of cells, it is not feasible to accurately evaluate the penetration, distribution or bystander killing patterns of ADCs. Besides, cells in 2D cultures, due to the lack of cell-cell and cell-matrix interactions, grow and behave differently from those growing in vivo in three dimensions. Therefore, 2D cultured cells, upon the treatment by ADCs, may respond differently from the same type of cells in vivo. These aspects limit the value of analysing results using 2D culture models, and promote the emerging of three-dimensional (3D) cell culturing techniques.
Comparison between 2D and 3D cell culture models for the analysis of ADCs
2D vs. 3D |
2D Cell Culture |
3D Cell Culture |
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Different from 2D culturing, 3D cell culturing techniques grow cells in 3D environments by using diverse natural or artificial extracellular matrix and/or scaffolds. Although it is more laborious and technically challenging to establish a 3D culture model compared with 2D cultures, the 3D culture system is biophysically and biochemically much more similar to in vivo tissues/organs, with the feasibility to mimic in vivo microenvironment, as well as cell-cell and cell-matrix interactions. As it is possible to generate solid tumor spheroid or micro-tissue models via 3D culturing techniques, the tissue penetration and bystander killing efficiency of ADCs can be assessed using these in vitro models. Moreover, the heterogeneous distribution of drugs in 3D tissue/tumor models may provide better indication of the in vivo drug distribution gradient.
Simplified scheme comparing in vitro analysis of therapeutic agents using 2D and 3D models.
With expertise and years of experiences in in vitro analysis, Creative Biolabs provides comprehensive analysis of ADCs using both 2D and 3D culture models. The advanced 3D cell culture platform at Creative Biolabs enables the thorough assessment of ADCs, including their targeting ability, tumor penetration and internalization efficiency, as well as killing and bystander killing capacity. Through in-depth comparison between 2D and 3D analysing results, our science team at Creative Biolabs also provides customers with advices on the design and optimization of ADC products before in vivo tests. This advanced 2D vs. 3D comparative analysis service can significantly reduce the requirement for repeating in vivo assessments after every redesigning or optimization steps for producing highly efficient ADCs. Please contact us for more information and a detailed quote.
Reference:
- Adjei, I. M.; Blanka, S. Modulation of the tumor microenvironment for cancer treatment: a biomaterials approach. J. Funct. Biomater. 2015, 6, 81-103.
For Research Use Only. NOT FOR CLINICAL USE.
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