Scientists have 3D bioprinted a vascularized tumor and successfully treated it with immunotherapy
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For the first time, Scientists have 3D bioprinted a vascularized tumor and successfully treated it with immunotherapy.
In recent years, breakthroughs have been made in the field of cancer therapy, but standardized and physiologically relevant in vitro testing platforms are still lacking. A key hurdle is the complex interplay between the tumor microenvironment and the immune response.
Therefore, researchers in this field have to rely on clinical trials to test the therapeutic effect, which ultimately limits the successful clinical translation of anticancer therapeutic drugs.
Recently, in a new study published in “Advanced Functional Materials” , a research team led by Penn State University has developed for the first time a dynamic flow-based 3D bioprinted multi-scale vascularized breast tumor model that can respond to chemotherapy drugs and immunotherapy react.
The study helps scientists understand how human immune cells interact with solid tumors and lays the foundation for the precise development of tumor models.
The use of animal experiments may no longer be necessary in the research and development of future anticancer therapies.
Immunotherapy has proven to be a promising approach in the treatment of hematological malignancies.
Essentially, the approach involves taking a patient’s immune cells out of the body and genetically editing them to be cytotoxic to cancer cells before reintroducing them into the patient’s bloodstream.
The engineered CAR-T cells need to move throughout the body, so circulation is critical. For tumors, however, this efficient cycle does not exist, so the team developed new tumor models in an attempt to better understand how tumors respond to immunotherapy.
According to the data released by the World Health Organization, breast cancer has replaced lung cancer as the number one cancer in the world. In 2020 alone, there will be as many as 2.26 million new cases worldwide.
In the new study, the team investigated CAR-T-induced cytotoxicity for the first time in the vascularized and dynamically flowing breast tumor microenvironment.
Using suction-assisted bioprinting, heterogeneous tumors composed of human endothelial cells, cancer cells, and fibroblasts were precisely bioprinted at specific locations in the central vasculature.
The addition of endothelial cells to cancer cells vascularizes the tumor, providing an ideal co-culture model for studying tumor-endothelial interactions in vitro.
RNA-sequencing of the heterogeneous tumor microenvironment revealed upregulated genes in tumor models that positively affected metastasis and angiogenesis in the presence of human dermal fibroblasts.
In this vascularized and dynamic tumor microenvironment, researchers effectively studied the efficacy of chemotherapy and CAR-T cell-based immunotherapy.
They first tested the accuracy of the tumor model by infusing it for 72 hours with doxorubicin, an anthracycline chemotherapy drug commonly used to treat breast cancer .
The results showed that the 3D bioprinted tumors responded to chemotherapy, resulting in a dose-dependent reduction in tumor volume.
They then used human CAR-T cells designed to recognize the epidermal growth factor receptor 2 (HER2) on aggressive breast cancer cells.
After the gene-edited CAR-T cells circulated in the tumor for 72 hours, the researchers found that extensive CAR-T cell recruitment to endothelial cells, a large number of T cell activation and infiltration into the tumor site, resulting in an approximately 70% reduction in tumor volume .
Precise control over tumor spatial location confirmed that tumor distance from perfused vasculature affects tumor angiogenesis and cancer invasion, two cardinal hallmarks of cancer.
In conclusion, this study devised a method to study CAR-T interaction with solid tumors in the vascularized tumor microenvironment, thereby opening new avenues for understanding and developing more targeted therapeutic strategies.
Paper link:
https://dx.doi.org/10.1002/adfm.202203966
For the first time, Scientists have 3D bioprinted a vascularized tumor and successfully treated it with immunotherapy
(source:internet, reference only)
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