3D Bioprinted Breast Tumors for Immunotherapy Testing

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A team of scientists at Penn State has bioprinted breast tumor mimics with significant complexity, including a form of vascularization and the ability to precisely place cells in certain locations within the construct. The scientists used a technique called aspiration-assisted bioprinting to achieve this.

With many anti-cancer therapies failing at the clinical trial stage and the ethical considerations of animal studies, there is a need for better in vitro cancer models that allow for advanced therapeutic testing. The models have allowed the researchers to test advanced therapies, including CAR-T immune cell therapies.

Chimeric antigen receptor (CAR) T-cells represent a sophisticated anti-cancer therapy. The T cells are genetically modified so that they can seek out and destroy tumors, but testing their efficacy in realistic in vitro models has been a challenge to date. Thankfully, in vitro tumor models are getting more sophisticated and this latest bioprinting technology has allowed researchers to investigate the tumor destroying abilities of these cells by enabling ‘vascularization’ within the printed constructs, meaning the cells can circulate within.

“Immunotherapy has already been shown to be a promising treatment for hematologic malignancies,” said Ibrahim Ozbolat, a researcher involved in the study. “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 tumors, that kind of effective circulation doesn’t exist, so we built our model to try to better understand how tumors respond to immunotherapy.”

To create the printed constructs, the researchers used a technique called aspiration-assisted bioprinting. The method allows the researchers to precisely deposit tumor spheroids or other engineered cell constructs into a gel substrate. This lets them arrange components precisely so that they are in a specific orientation and proximity to each other. In this instance, the researchers used the technique to create a proxy vasculature and deposit tumor spheroids near this vasculature. It also allowed them to introduce CAR-T cells into the construct to determine if they could destroy the tumors.  

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

Study in Advanced Functional Materials: Chemotherapeutics and CAR‐T Cell‐Based Immunotherapeutics Screening on a 3D Bioprinted Vascularized Breast Tumor Model

Via: Penn State


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