1. Chemotherapeutics and CAR‐T Cell‐Based Immunotherapeutics Screening on a 3D Bioprinted Vascularized Breast Tumor Model.
- Author
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Dey, Madhuri, Kim, Myoung Hwan, Dogan, Mikail, Nagamine, Momoka, Kozhaya, Lina, Celik, Nazmiye, Unutmaz, Derya, and Ozbolat, Ibrahim T.
- Subjects
BREAST ,BREAST tumors ,MEDICAL screening ,CHIMERIC antigen receptors ,T cells ,INDIVIDUALIZED medicine - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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