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

Abstract

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.