Tumor is not a collection of simple cancerous cells, but rather a complex tissue composed of various types of cells under unique tumor microenvironment (TME). As our understanding of cancer is deepen, it becomes clear that interrogating cancer cell alone is not enough to fully understand various interactions between tumor cells and other types of cells in TME ( for example, an immunosuppressive environment established by tumor cells and immune cells). There has been steady progress in improving ex vivo cell culture system to mimic the TME in order to test various treatment moieties. However, it is remaining as a major hurdle to design an assay system that is 1) manageable enough to perform in conventional cell culture facility and 2) types of cells using and 3) flexible enough to test both human and mouse cell types.

In Txinno Bioscience, we developed two platform technologies to address these issues and facilitate our drug development process.

 

1) TxLfinder^® is a technology that evaluates the infiltration of immune cells (PBMCs) into 3D tumor spheroids. by co-culturing cancer cell line-derived spheroids and immune cells, separated by a microporous membrane under ex vivo conditions

2) TxTquantifier^® is a technology that evaluates immune cell-mediated cytotoxicity against cancer cell line-derived 3D spheroids under ex vivo conditions, specifically measuring the increased cancer cell death induced by drug treatment during co-culture with PBMCs.

TxLfinder^® by Txinno Bioscience  can be a highly useful ex vivo culture system to measure the infiltration of immune by innate immune modulator reflecting conversion of TIL-deficient “cold tumor” to TIL-proficient “hot tumor” and to access the efficacy of IO drugs of various mode of action.

TxTquantifier^® developed by Txinno Bioscience can be used to test various anti-cancer therapeutics, including chemical compound, biologics as well as cell therapy. Also, the system can be used to perform various genetic screening using genomic reagents, like CRISPR, to find the next generation cancer targets.

TxLfinder^® / TxTquantifier^® with human-derived cancer cells and immune cells (Version 1) was upgraded into a system can culture spheroid of cancer cells and CAF (cancer-associated fibroblast) with immune cells (Version 2). For next step, we are developing a co-culture system with cancer cells, CAFs, endothelial cells and extracellular matrix (Version 3), which closely mimic actual tumor microenvironment (TME) of patient tumors.

The human proteome comprises approximately 20,000 proteins, and dysregulation—such as aberrant post-translational modifications or pathological overexpression—can lead to disease. To maintain protein homeostasis, cells employ highly coordinated protein quality-control mechanisms that selectively tag dysfunctional or superfluous proteins for degradation.

Conventional targeted therapies primarily function by binding to pathogenic proteins to modulate or inhibit their activity. In contrast, Targeted Protein Degradation (TPD) technologies eliminate the disease-causing protein altogether by leveraging the cell’s endogenous degradation machinery. One such modality, PROteolysis-TArgeting Chimeras (PROTACs), exploits the ubiquitin–proteasome system (UPS) to induce ubiquitination and subsequent proteasomal degradation of specific target proteins.

PROTAC offers several advantages, including the ability to address previously “undruggable” targets, achievement of complete target protein ablation, and reduced dosing requirements compared with conventional inhibitors, thereby lowering the likelihood of dose-related toxicities.

Txinno Bioscience has established an AI-enabled PROTAC discovery platform, TxPchider^®, designed to accelerate therapeutic development against traditionally undruggable proteins. This technology is an AI-based platform designed to develop novel PROTAC molecules by designing new linkers that connect target protein binders with E3 ligase binders, while optimizing drug-like properties.