Chemotherapeutics and CAR-T Cell-Based Immunotherapeutics Screening on a 3D Bioprinted Vascularized Breast Tumor Model

Document Type

Article

Publication Date

10-3-2022

Publication Title

Advanced Functional Materials

Keywords

JGM, bioprinting, cancer, CAR-T immunotherapy, tumor models

JAX Source

Advanced Functional Materials. 2022;32(52):2203966.

Volume

32

Issue

52

First Page

2203966

ISSN

1616-3028

DOI

https://doi.org/10.1002/adfm.202203966

Grant

This work was supported by NSF awards 1914885 (I.T.O.) and 1624515 (I.T.O.), H. G. Barsumian, M.D. Memorial Fund (I.T.O.), 2236 CoCirculation2 of TUBITAK award 121C359 (I.T.O.), NCI R21 CA224422 01A1 (I.T.O. and D.U.), and NCI P30 CA034196 (D.U.). The opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by NSF, TUBITAK, and NCI.

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.

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