鑫品免疫細胞 -- 鑫品於國際期刊「Journal of Hematology & Oncology」發表研究成果
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鑫品於國際期刊「Journal of Hematology & Oncology」發表研究成果

Phenotype and functional evaluation of ex vivo generated antigen-specific immune effector cells with potential for therapeutic applications
Shuhong Han1, Yuju Huang2, Yin Liang2, Yuchin Ho2, Yichen Wang2 and Lung-Ji Chang*1

Published: 6 August 2009
Journal of Hematology & Oncology 2009, 2:34 doi:10.1186/1756-8722-2-34
Received: 30 June 2009
Accepted: 6 August 2009
This article is available from: http://www.jhoonline.org/content/2/1/34
 

ABSTRACT
Ex vivo activation and expansion of lymphocytes for adoptive cell therapy has demonstrated great success. To improve safety and therapeutic efficacy, increased antigen specificity and reduced non-specific response of the ex vivo generated immune cells are necessary. Here, using a complete protein-spanning pool of pentadecapeptides of the latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV), a weak viral antigen which is associated with EBV lymphoproliferative diseases, we investigated the phenotype and function of immune effector cells generated based on IFN-γ or CD137 activation marker selection and dendritic cell (DC) activation. These ex vivo prepared immune cells exhibited a donor- and antigen-dependent T cell response; the IFN-γ-selected immune cells displayed a donor-related CD4- or CD8-dominant T cell phenotype; however, the CD137-enriched cells showed an increased ratio of CD4 T cells. Importantly, the pentadecapeptide antigens accessed both class II and class I MHC antigen processing machineries and effectively activated EBV-specific CD4 and CD8 T cells. Phenotype and kinetic analyses revealed that the IFN-γ and the CD137 selections enriched more central memory T (Tcm) cells than did the DC-activation approach, and after expansion, the IFN-γ-selected effector cells showed the highest level of antigen-specificity and effector activities. While all three approaches generated immune cells with comparable antigen-specific activities, the IFN-γ selection followed by ex vivo expansion produced high quality and quantity of antigen-specific effector cells. Our studies presented the optimal approach for generating therapeutic immune cells with potential for emergency and routine clinical applications.



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