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

Adv Drug Deliv Rev. 2022 Mar:182:114111. doi: 10.1016/j.addr.2022.114111. Epub 2022 Jan 11.

Abstract

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Age Factors
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Cell Culture Techniques, Three Dimensional
  • Drug Liberation
  • Drug Screening Assays, Antitumor / methods*
  • Immune System / immunology*
  • Models, Biological
  • Neoplasms / drug therapy*
  • Neoplasms / physiopathology*
  • Sex Factors
  • Tissue Engineering / methods*

Substances

  • Antineoplastic Agents