IMR Press / FBL / Volume 25 / Issue 2 / DOI: 10.2741/4806

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo
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1 ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806
2 Forevertek Biotechnology Co.,Ltd, Building M0, Oversea Graduate Park National High-tech Industrial Zone, 410003, Changsha, PRC
3 Oklahoma Health SciencesCenter, University of Oklahoma, Oklahoma City, OK, 73101
Front. Biosci. (Landmark Ed) 2020, 25(2), 270–282; https://doi.org/10.2741/4806
Published: 1 January 2020
(This article belongs to the Special Issue FAK signaling)
Abstract

Chimeric antigen receptor (CAR) T cell immunotherapy has demonstrated clinical success in treatment of B-cell hematologic cancers. In this study, we compared human Transferrin epitope tagged CAR-T cells with non-tagged CAR-T cells for cytotoxicity, IFN-gamma secretion and tumor clearance in NSG mice. CD19-TF-CAR-T cells had similar cytotoxicity in vitro to CD19-CAR-T cells against cells expressing CD19 antigen: exogenously CD19+ Hela cells and endogenously CD19+ Raji cells. In addition, CD22-TF CAR-T cells were similarly cytotoxic against CD22+ CHO cells and CD22+ Raji cells. Both CD19-TF or CD22-TF-CAR-T cells secreted less IFN-gamma as compared to non-tagged CAR-T cells. In a Raji xenograft NSG mouse model, CD19-TF-CAR-T cells were as effective as CD19-CAR-T cells in reducing tumor growth and extending mouse survival. The results show that CD19-TF-CAR-T cells can be monitored using TF antibody in vitro and ex vivo, and that these cells effectively killed Raji cells in vitro and in vivo with reduced secretion of IFN-gamma. Thus, these TF-tagged CAR-T cells might have improved safety and provide a basis for future clinical studies.

Keywords
Chimeric Antigen Receptor
Immunotherapy
Epitope
Transferrin
CD19
CD22
Figures
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