Related Experiment Video
Updated: Jun 22, 2025
Direct Bioprinting of 3D Multicellular Breast Spheroids onto Endothelial Networks
Published on: November 2, 2020
Chemotherapeutics and CAR-T Cell-Based Immunotherapeutics Screening on a 3D Bioprinted Vascularized Breast Tumor
Madhuri Dey1, Myoung Hwan Kim2, Mikail Dogan3
1Department of Chemistry, Penn State University, University Park, PA 16802, USA; The Huck Institutes of the Life Sciences, Penn State University, University Park, PA 16802, USA.
Abstract:
Despite substantial advancements in development of cancer treatments, lack of standardized and physiologically-relevant in vitro testing platforms limit the early screening of anticancer agents. A major barrier is the complex interplay between the tumor microenvironment and immune response. To tackle this, a dynamic-flow based 3D bioprinted multi-scale vascularized breast tumor model, responding to chemo and immunotherapeutics is developed. Heterotypic tumors are precisely bioprinted at pre-defined distances from a perfused vasculature, exhibit tumor angiogenesis and cancer cell invasion into the perfused vasculature. Bioprinted tumors treated with varying dosages of doxorubicin for 72 h portray a dose-dependent drug response behavior. More importantly, a cell based immune therapy approach is explored by perfusing HER2-targeting chimeric antigen receptor (CAR) modified CD8+ T cells for 24 or 72 h. Extensive CAR-T cell recruitment to the endothelium, substantial T cell activation and infiltration to the tumor site, resulted in up to ≈70% reduction in tumor volumes. The presented platform paves the way for a robust, precisely fabricated, and physiologically-relevant tumor model for future translation of anti-cancer therapies to personalized medicine.
Insights
A novel 3D bioprinted breast tumor model with vasculature enables testing of chemotherapy and CAR-T cell immunotherapy, showing significant tumor reduction and paving the way for personalized cancer treatments.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Immunotherapy
Background:
- Current in vitro cancer models lack physiological relevance, hindering anticancer agent screening.
- The tumor microenvironment and immune response interplay is a key challenge in cancer therapy development.
Purpose of the Study:
- To develop a dynamic-flow based 3D bioprinted vascularized breast tumor model.
- To assess the model's response to chemotherapy and chimeric antigen receptor (CAR) T-cell immunotherapy.
Main Methods:
- Precise bioprinting of heterotypic tumors adjacent to perfused vasculature.
- In vitro testing of doxorubicin for dose-dependent response.
- Perfusion of HER2-targeting CAR T-cells to evaluate immune therapy efficacy.
Main Results:
- The model demonstrated tumor angiogenesis and cancer cell invasion into vasculature.
- Doxorubicin treatment showed a dose-dependent response.
- CAR T-cell therapy led to significant T-cell recruitment, activation, infiltration, and up to 70% tumor volume reduction.
Conclusions:
- The developed 3D bioprinted tumor model is a robust and physiologically relevant platform.
- This model facilitates the translation of anti-cancer therapies towards personalized medicine.
- It offers a promising tool for evaluating both chemotherapeutics and immunotherapeutics.
