Oncotarget

Research Papers:

Simultaneous in vitro generation of CD8 and CD4 T cells specific to three universal tumor associated antigens of WT1, survivin and TERT and adoptive T cell transfer for the treatment of acute myeloid leukemia

Hyun-Jung Sohn, Ji Yoon Lee, Hyun-Joo Lee, Dae-Hee Sohn, Hyun-Il Cho, Hee-Je Kim _ and Tai-Gyu Kim

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Oncotarget. 2017; 8:44059-44072. https://doi.org/10.18632/oncotarget.17212

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Abstract

Hyun-Jung Sohn1,6,*, Ji Yoon Lee2,5,*, Hyun-Joo Lee1,6, Dae-Hee Sohn4,6, Hyun-Il Cho1,2, Hee-Je Kim2,3 and Tai-Gyu Kim1,4

1Catholic Hematopoietic Stem Cell Bank, The Catholic University of Korea, Seoul, Korea

2Leukemia Research Institute, Seoul St. Mary`s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

3Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary`s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

4Departments of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Korea

5Department of Biomedical Laboratory Science, College of Health Sciences, Sangji University, Wonju, Korea

6ViGenCell Inc., Seoul, Korea

*These authors have contributed equally to this work

Correspondence to:

Hee-Je Kim, email: [email protected]

Tai-Gyu Kim, email: [email protected]

Keywords: Wilms’ tumor protein 1, survivin, telomerase reverse transcriptase, dendritic cells, adoptive T cell therapy

Received: December 21, 2016    Accepted: March 03, 2017    Published: April 19, 2017

ABSTRACT

Previously, we found that most patients with acute myeloid leukemia (AML) expressed at least one of the leukemic associated antigens (LAAs) WT1, survivin and TERT, and different combinations of the three LAAs predicted negative clinical outcomes. Multi-tumor antigen-specific T cells were generated to overcome antigenic variation and may be sufficient to maximize antitumoral effects. To generate triple antigen-specific (Tri)-T cells that recognize three LAAs, dendritic cells (DCs) were transfected with three tumor antigen-encoding RNAs. These DCs were used to stimulate both CD8 and CD4 T cells and to overcome the limitation of known human leukocyte antigen-restricted epitopes. The sum of the antigen-specific T cell frequencies was higher in the Tri-T cells than in the T cells that recognized a single antigen. Furthermore, the Tri-T cells were more effective against leukemic blasts that expressed all three LAAs compared with blasts that expressed one or two LAAs, suggesting a proportional correlation between IFN-γ secretion and LAA expression. Engrafted leukemic blasts in the bone marrow of mice significantly decreased in the presence of Tri-T cells. This technique represents an effective immunotherapeutic strategy in AML.


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