In vitro 3D cell culture technology

One of the key challenges in drug development is often attributable to failures due to efficacy and safety issues. For instance, together with safety failure in clinical phase, in vivo toxicology outcome in pre-clinical phase can hamper the process to develop new compounds. In the last years, the industry has heavily invested to tackle the problem of subsequent toxicology-related attrition and to gain better understanding of mechanisms before to reach in vivo studies or the clinical phase.

Advanced cell models like in vitro 3D cell culture technologies can help to address these issues in pre-clinical phase. The necessity of using more translational, human-relevant and predictive models such as in vitro 3D cell culture technologies can enhance clinical efficacy prediction. Moreover, human in vitro models help to reduce the attrition rate due to species specificities.

Preclinical cancer modeling

In oncology, drug development process has to consider challenges including tumor heterogeneity, microenvironment complexity, immune and metabolic response heterogeneity, and drug resistance.
Sometimes in vivo models cannot be so reliable due to differences in immune system and drug metabolism. Patient-derived xenograft (PDX) models with tumors transplanted from patient into immunocompromised mice can circumvent immune rejection, but mouse stromal composition can progressively becomes dominant. Immunocompromised models can be useful mainly for testing the efficacy of chemotherapeutics and targeted small-molecule inhibitors. For evaluating immunomodulatory therapies, mice can be engineered to generate tumors -Genetically Engineered Mice (GEM) or alternatively, tumors harvested from GEMs can be transplanted and expanded into fully immunocompetent hosts, creating GEM-Derived Allograft (GDA) models. Also if Genetically Engineered Mouse (GEM) represents the current in vivo platform for immunomodulatory therapies, no model can perfectly capture the human condition. Technologies to “humanize” the mouse immune system are still far from routine or patient-specific applications.

In vitro 3D cell culture technologies like VITVO could help to overcome these limitations. Aside from the 3Rs rule that leads to find models alternative to animals, a great advantage of in vitro 3D cell culture technologies is represented by the capability to study a human and not “humanized” system (e.g. patient-derived unfractioned tumor cells with TILs), which helps to obtain more predictive and reliable data.