World’s First Long-Term Colorectal Cancer Model by 3D Bioprinting as a Mechanism for Screening Oncolytic Viruses

SIMPLE SUMMARY: Although many new cancer drugs look like they are working in the laboratory, they fail when tested on real people. This is often because the cancer cell models they are tested on are short-term, but cancer grows in people over a longer period, and things change over time. This is not a criticism of cancer laboratories, but more a realism of the limits of scientific research. This is why we developed this longer-lasting model of colorectal cancer that has moved around the body. At the same time, we used this model to test next-generation delivery of chemotherapy drugs to tumors with an advanced targeting virus. All levels of cancer research have value, both short-term and long-term, but the longer strategies need to catch up, so this study demonstrates what can be achieved with 3D bioprinting tumor models and testing viruses transformed for good. ABSTRACT: Long-term modelization of cancer as it changes in the human body is a difficult goal, particularly when designing and testing new therapeutic strategies. This becomes even more difficult with metastasis modeling to show chemotherapeutic molecule delivery directly to tumoral cells. Advanced therapeutics, including oncolytic viruses, antibody-based and cell-based therapies are increasing. The question is, are screening tests also evolving? Next-generation therapeutics need equally advanced screening tests, which whilst difficult to achieve, are the goal of our work here, creating models of micro- and macrotumors using 3D bioprinting. We developed advanced colorectal cancer tumor processing techniques to provide options for cellular expansion, microtumor printing, and long-term models, which allow for the evaluation of the kinetics of penetration testing, therapeutic success, targeted therapies, and personalized medicine. We describe how we tested tumors from a primary colorectal patient and, applying 3D bioprinting, matured long-term models for oncolytic metastatic screening. Three-dimensional microtumors were kept alive for the longest time ever recorded in vitro, allowing longitudinal studies, screening of oncolytic viruses and realistic modelization of colorectal cancer. These 3D bioprinted models were maintained for around 6 months and were able to demonstrate the effective delivery of a product to the tumoral environment and represent a step forward in therapeutic screening.