Baru, A. | bioRxiv Science

bioRxiv2020

Recapitulating tumor microenvironment using preclinical 3D tissueoids model for accelerating cancer research and drug screening

The formation of three-dimensional spheroid tumor model using the scaffold-based platforms has been demonstrated over many years now. 3D tumor models are generated mainly in non-scalable culture systems, using synthetic and biological scaffolds. Many of these models fail to reflect the complex tumor microenvironment and do not allow long-term monitoring of tumor progression. This has resulted in inconsistent data in drug testing assays during preclinical and clinical studies. To overcome these limitations, we have developed 3D tissueoids model by using novel AXTEX-4D platform. Cancer 3D tissueoids demonstrated the basic features of 3D cell culture with rapid attachment, proliferation, and longevity with contiguous cytoskeleton and hypoxic core. This study also demonstrated greater drug resistance in 3D-MCF-7 tissueoids in comparison to 2D monolayer cell culture and the collagen-based 3D system. In conclusion, 3D-tissueoids are more responsive than 2D-cultured cells in simulating important tumor characteristics, anti-apoptotic features, and their resulting drug resistance.

cancer biology↗

bioRxiv2020

AXTEX-4D™: A Novel 3D ex vivo platform for preclinical investigations of immunotherapy agents

The latest advancements in oncology are majorly focused on immuno-oncology (I-O) therapies. However, only ~7% of drugs are being approved from the preclinical discovery phase to phase 1. The most challenging issues in I-O is the problem of developing active and efficient drugs economically and on time. This mandates an urgent need for better preclinical screening models that closely mimic the in vivo tumor microenvironment. The established and most common methods for investigating the tumoricidal activity of I-O drugs are either two-dimensional (2D) systems or primary tumor cells in standard tissue culture vessels. However, they do not mimic the tumor microenvironment. Therefore, the more in vivo-like three-dimensional (3D) multicellular tumor spheroids are quickly becoming the favored model to examine immune cell-mediated responses in reaction to the administration of I-O drugs. Accordingly, we have demonstrated the utility of the three-dimensional ex vivo oncology model, developed on our novel AXTEX-4D platform to assess therapeutic efficacies of I-O drugs by investigating immune cell proliferation, migration, infiltration, cytokine profiling, and cytotoxicity of tumor tissueoids. The platform eliminates the need for additional biomolecules such as hydrogels and instead relies on the cancer cells themselves to create their own gradients and microenvironmental factors. In effect, the more comprehensive and in vivo like immune-oncology model developed on AXTEX-4D platform can be utilized for high-throughput screening of immunotherapeutic drugs.

immunology↗