Expression of chimeric receptor CD4ζ by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo.
Expression of chimeric receptor CD4ζ by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo.
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DOI：
10.1002/stem.1611
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发表时间：
2014-04
期刊：
影响因子：
5.2
通讯作者：
Kaufman, Dan S.
中科院分区：
文献类型：
--
作者：
Ni, Zhenya;Knorr, David A.;Bendzick, Laura;Allred, Jeremy;Kaufman, Dan S.
关键词：
Cell-based immunotherapy has been gaining interest as an improved means to treat HIV/AIDS. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) could become a potential resource. Our previous studies have shown hESC and iPSC-derived natural killer (NK) cells can inhibit HIV-infected targets in vitro. Here, we advance those studies by expressing a HIV chimeric receptor combining the extracellular portion of CD4 to the CD3ζ intracellular signaling chain. We hypothesized that expression of this CD4ζ receptor would more efficiently direct hESC- and iPSC-derived NK cells to target HIV-infected cells. In vitro studies showed the CD4ζ expressing hESC- and iPSC-NK cells inhibited HIV replication in CD4+ T cells more efficiently than their unmodified counterparts. We then evaluated CD4ζ-hESC- and iPSC-NK cells in vivo anti-HIV activity using a humanized mouse model. We demonstrated significant suppression of HIV replication in mice treated with both CD4ζ-modified and unmodified hESC-/iPSC-NK cells compared to control mice. However, we did not observe significantly increased efficacy of CD4ζ expression in suppression of HIV infection. These studies indicate that hESC/iPSC-based immunotherapy can be utilized as a unique resource to target HIV/AIDS.
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影响因子：
15.3
作者：
Crotta, Stefania;Stilla, Annalisa;Wack, Andreas;D'Andrea, Annalisa;Nuti, Sandra;D'Oro, Ugo;Mosca, Marta;Filliponi, Franco;Brunetto, R Maurizia;Bonino, Ferruccio;Abrignani, Sergio;Valiante, Nicholas M
通讯作者：
Valiante, Nicholas M
影响因子：
11.2
作者：
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通讯作者：
Malmberg, Karl Johan
DOI：
10.1084/jem.20052507
发表时间：
2006-04-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Freud AG;Yokohama A;Becknell B;Lee MT;Mao HC;Ferketich AK;Caligiuri MA
通讯作者：
Caligiuri MA
影响因子：
12.4
作者：
Deeks, SG;Wagner, B;Hege, KM
通讯作者：
Hege, KM
影响因子：
20.3
作者：
Grzywacz, Bartosz;Kataria, Nandini;Verneris, Michael R.
通讯作者：
Verneris, Michael R.