4.7 Review

Engineering in vitro immune-competent tissue models for testing and evaluation of therapeutics

Journal

ADVANCED DRUG DELIVERY REVIEWS
Volume 182, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.addr.2022.114111

Keywords

Tumor; Drug screening; Autoimmunity; Vaccine screening; Lymphatics; Organ-on-chip; Preclinical; Engineered T cells

Funding

  1. National Institute of Biomedical Imaging and Bioengineering (NIBIB) through the National Institutes of Health (NIH) [U01EB029127]
  2. National Center for Advancing Translational Sciences (NCATS)
  3. National Cancer Institute [R37CA222563]
  4. National Institute of Allergy and Infectious Diseases [R01AI131723]
  5. Institute for Critical Technology and Applied Science Scholarship through Virginia Tech
  6. Graduate Research Fellowship Program through the National Science Foundation (NSF)

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Advancements in 3D cell culture, microscale fluidic control, and cellular analysis have allowed for the development of more physiologically-relevant engineered models of human organs. However, these models often overlook the important role of the immune system. This review discusses key components to consider in designing immune-competent models and reviews recent applications of immune models for cancer therapeutics screening, engineered T cell evaluation, autoimmune disease modeling, and vaccine efficacy screening.
Advances in 3D cell culture, microscale fluidic control, and cellular analysis have enabled the development of more physiologically-relevant engineered models of human organs with precise control of the cellular microenvironment. Engineered models have been used successfully to answer fundamental biological questions and to screen therapeutics, but these often neglect key elements of the immune system. There are immune elements in every tissue that contribute to healthy and diseased states. Including immune function will be essential for effective preclinical testing of therapeutics for inflammatory and immune-modulated diseases. In this review, we first discuss the key components to consider in designing engineered immune-competent models in terms of physical, chemical, and biological cues. Next, we review recent applications of models of immunity for screening therapeutics for cancer, preclinical evaluation of engineered T cells, modeling autoimmunity, and screening vaccine efficacy. Future work is needed to further recapitulate immune responses in engineered models for the most informative therapeutic screening and evaluation.(c) 2022 Elsevier B.V. All rights reserved.

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