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

Cancers (Basel). 2023 Sep 26;15(19):4724. doi: 10.3390/cancers15194724.

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.

Keywords: 3D bioprinting; colorectal; longitudinal; oncolytic virus.

Grants and funding

This work was supported by the Fonds Unique Interministériel (FUI)—Banque Publique de l’Innovation (BPI) France, Metropoles of Lyon, and Grenoble, Lyonbiopole, Minalogic and La Région Auvergne-Rhône-Alpes (AAP-23 3D ONCOCHIP, No. DOS0062033/0). CTIBIOTECH is supported by the Auvergne-Rhône Alpes Region for its production platform of microtumors by 3D-bioprinting for cancer research (Future-oriented PIA3 investment programs, “Transformation of SMEs through innovation” prize). This study is financed by the European Union-NextGenerationEU, through the National Recovery and Resilience Plan of the Republic of Bulgaria, project No. BG-RRP-2.004-0007-C01.