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New 3D bioprinted breast cancer model could aid immunotherapy development

Penn State researchers have successfully created breast cancer tumours using 3D bioprinting. The work, covered in two papers published in the journals Biofabrication and Advanced Functional Materials, paves the way for improved cancer therapies that do not rely on the use of “in vivo” experiments.

Bioprinting breast cancer

Despite recent advances in the cancer therapy space, there are still very few pre-clinical platforms available for studying experimental anticancer agents. Instead, researchers are forced to rely on clinical trials to test new developments, and this can significantly limit successful translation to the clinic.

To overcome this challenge, Ibrahim Ozbolat and his team at Penn State University have developed 3-dimensional bioprinted models of tumours for studying potential cancer treatments. Their lab, which specialises in 3D bioprinting of a range of human tissues, used a technique called aspiration-assisted bioprinting for their most recent work. This allowed them to precisely locate tumours in 3D and form a multi-scale vascularised breast cancer model.

“Our model is made from human cells, but what we make is a very simplified version of the human body,” Ozbolat said. “There are many details that exist in the native microenvironment that we aren’t able to replicate, or even consider replicating. We are aiming for simplicity within complexity. We want to have a fundamental understanding of how these systems work — and we need the growth process to be streamlined, because we don’t have time to wait for tumours to grow at their natural pace.”

The result is a bioprinted model of breast cancer that could open new doors to understanding the tumour microenvironment and the body’s immune response.

Testing treatments

To test whether the model would be useful (and accurate) for future cancer research, the team first treated it with doxorubicin, and anthracycline-based chemotherapeutic drug commonly used for breast cancer treatment. They observed a dose-dependent drug response to this treatment, so decided to move on to testing a cell-based immunotherapeutic drug.

“Immunotherapy has already been shown to be a promising treatment for hematologic malignancies,” Ozbolat said. “Essentially, immune cells of the patient are removed and gene-edited to be cytotoxic for cancer cells, then reintroduced into the patient’s bloodstream. Circulation is critical because the altered cells need to move around the body. With tumours, that kind of effective circulation doesn’t exist, so we built our model to try to better understand how tumours respond to immunotherapy.”

They created CD8+ T cells genetically engineered to express mucosal-assisted invariant T (MAIT) cell receptors and watched how their models responded after 24 and 72 hours. After 72 hours, the cells in the bioprinted tumour had generated a positive immune response – there was extensive CAR-T cell recruitment to the endothelium, substantial T cell activation and infiltration to the tumour site, and a 70% reduction in tumour volumes.

Looking ahead

Building on their successful findings, the team plans to now look at tumours removed from actual breast cancer patients to see how the varying treatments respond – still an important step in understanding the intricacies of a complex disease like cancer. Nevertheless, their new model lays the foundation for precision fabrication of tumour models and offers researchers that crucial first step in determining effective treatment strategies for cancer patients.  

“We’ve developed a tool that serves as a clinical test platform to safety and accurately evaluate experimental therapies,” said Ozbolat. “It is also a research platform for immunologists and biologists to understand how the tumour grows, how it interacts with human cells, and how it metastasizes and spreads in the body.”

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