Engineered Ovarian Cancer Cell Lines for Validation of CAR T Cell Function

Adv Biosyst. 2020 Jan;4(1):e1900224. doi: 10.1002/adbi.201900224. Epub 2019 Nov 29.

Abstract

A set of genetically engineered isogenic cell lines is developed to express either folate receptor alpha or mesothelin, and a control cell line negative for both antigens. These cell lines also express fluorescent and bioluminescent reporter transgenes. The cell lines are used to authenticate specificity and function of a T-cell biofactory, a living vector that is developed to express proportionate amounts of engineered proteins upon engaging with disease cells through their specific antigenic biomarkers. The engineered cell lines are also used to assess the cytolytic function and specificity of primary T cells engineered with chimeric antigen receptors; and the specificity of monoclonal antibodies. The strategy described can be used to generate other cell lines to present different disease-specific biomarkers for use as quality control tools.

Keywords: CAR T cells; artificial antigen presenting cell; authentication of biologics; cell engineering; quality control.

Publication types

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

MeSH terms

  • Cell Engineering / methods*
  • Cell Line, Tumor
  • Female
  • Genetic Engineering / methods*
  • Humans
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Receptors, Chimeric Antigen / genetics*
  • Receptors, Chimeric Antigen / metabolism
  • T-Lymphocytes* / cytology
  • T-Lymphocytes* / metabolism

Substances

  • Receptors, Chimeric Antigen