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Front Biosci (Landmark Ed). 2020 Jan 1;25:270-282.

Transferrin epitope-CD19-CAR-T cells effectively kill lymphoma cells in vitro and in vivo.

Author information

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, China.
3
Promab Biotechnologies, 2600 Hilltop Drive, Building B, Richmond, CA 94806.
4
ProMab Biotechnologies, 2600 Hilltop Drive, C320, Richmond, CA, 94806, vita.gol@promab.com.

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.

PMID:
31585889

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