Engineered Microphysiological Systems for Testing Effectiveness of Cell-Based Cancer Immunotherapies
by
, ,
Marco Campisi
1,†, 
Sarah E. Shelton
1,2,†, 
Minyue Chen
1,3,
Roger D. Kamm
2,4,
David A. Barbie
1 and
Erik H. Knelson
1,*
1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA
2
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
3
Department of Immunology, Harvard Medical School, Boston, MA 02115, USA
4
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2022, 14(15), 3561; https://doi.org/10.3390/cancers14153561
Submission received: 15 June 2022
/
Revised: 15 July 2022
/
Accepted: 16 July 2022
/
Published: 22 July 2022
(This article belongs to the Special Issue Biotechnological Approaches and Tools for the Development of Cancer Immunotherapeutics)
Simple Summary
Cell therapy has transformed oncology and drug development, yet better model systems are needed to recapitulate the tumor immune microenvironment (TIME). Microphysiological systems (MPS) can comprehensively model the human TIME, including immune cells, endothelial cells, fibroblasts, matrix, and cytokines. This review discusses current barriers to developing cell therapies for solid tumors from the perspective of MPS model design approaches. Overcoming current limitations in model systems and advancing MPS engineering will facilitate oncology drug development.
Abstract
Cell therapies, including adoptive immune cell therapies and genetically engineered chimeric antigen receptor (CAR) T or NK cells, have shown promise in treating hematologic malignancies. Yet, immune cell infiltration and expansion has proven challenging in solid tumors due to immune cell exclusion and exhaustion and the presence of vascular barriers. Testing next-generation immune therapies remains challenging in animals, motivating sophisticated ex vivo models of human tumor biology and prognostic assays to predict treatment response in real-time while comprehensively recapitulating the human tumor immune microenvironment (TIME). This review examines current strategies for testing cell-based cancer immunotherapies using ex vivo microphysiological systems and microfluidic technologies. Insights into the multicellular interactions of the TIME will identify novel therapeutic strategies to help patients whose tumors are refractory or resistant to current immunotherapies. Altogether, these microphysiological systems (MPS) have the capability to predict therapeutic vulnerabilities and biological barriers while studying immune cell infiltration and killing in a more physiologically relevant context, thereby providing important insights into fundamental biologic mechanisms to expand our understanding of and treatments for currently incurable malignancies.
Keywords:
microphysiological systems; cell therapy; immunotherapy; model systems; CAR T; CAR NK; microfluidics
