Open AccessReal-Time Killing Assays to Assess the Potency of a New Anti-Simian Immunodeficiency Virus Chimeric Antigen Receptor T Cell
Author(s) -
Françoise Haeseleer,
Karsten Eichholz,
Semih U. Tareen,
Nobuya Iwamoto,
Mario Roederer,
Frank Kirchhoff,
Haesun Park,
Afam A. Okoye,
Lawrence Corey
Publication year - 2020
Publication title -
aids research and human retroviruses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.993
H-Index - 92
eISSN - 1931-8405
pISSN - 0889-2229
DOI - 10.1089/aid.2020.0163
Subject(s) - chimeric antigen receptor , simian immunodeficiency virus , biology , virology , antigen , t cell , cytolysis , immunology , in vitro toxicology , virus , cytotoxicity , in vitro , immune system , biochemistry
The success of chimeric antigen receptor (CAR) T cell therapies for treating leukemia has resulted in a booming interest for the technology. Expression of a CAR in T cells allows redirection of their natural cytolytic activity toward cells presenting a specific designated surface antigen. Although CAR T cell therapies have thus far shown promising results mostly in B cell malignancy trials, interest in their potential to treat other diseases is on the rise, including using CAR T cells to control human immunodeficiency virus infection. The assessment of CAR T cell potency toward specific targets in vitro is a critical preclinical step. In this study, we describe novel assays that monitor the cytotoxicity of candidate CAR T cells toward simian immunodeficiency virus (SIV) infected CD4 T cells. The assays involve live cell imaging using a fluorescence microscopy system that records in real time the disappearance or appearance of targets infected with SIV carrying a fluorescent protein gene. The assays are highly reproducible, and their rapid turn around and reduced cost present a significant advance regarding the efficient preclinical evaluation of CAR T cell constructs and are broadly applicable to potential human diseases that could benefit from CAR T cell therapy.