NK cells are migrated and indispensable in the anti-tumor activity induced by CCL27 gene therapy.
Natural killer (NK) cells have been demonstrated could play an important role in the treatment of a number of tumors in mice. In the present study, chemokine CCL27, which be considered only selectively chemoattracts cutaneous lymphocyte antigen positive memory T cells and Langerhans cells, firstly demonstrated that it could induce the accumulation of NK cells into tumor by the intratumoral injection of CCL27-encoding fiber-mutant vector, AdRGD-CCL27. Experiments using spleen cell fractionation and RT-PCR showed CCL27 receptor, mCCR10, was strongly expressed in NK cells, suggesting the accumulation of NK cells in tumor was attributed to chemoattractant activity of CCL27 itself. Moreover, the combination of AdRGD-CCL27 and AdRGD-IL-12 induced the synergistic anti-tumor activity via NK-dependent manner and induced more NK cells infiltration into tumor nodule than that induced by AdRGD-CCL27 alone or AdRGD-IL-12 alone.
Gao
Jian-Qing
JQ
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou, Zhejiang, 310058, China. gaojianqing1029@yahoo.com.cn
Tsuda
Yasuhiro
Y
Han
Min
M
Xu
Dong-Hang
DH
Kanagawa
Naoko
N
Hatanaka
Yutaka
Y
Tani
Yoichi
Y
Mizuguchi
Hiroyuki
H
Tsutsumi
Yasuo
Y
Mayumi
Tadanori
T
Okada
Naoki
N
Nakagawa
Shinsaku
S
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D054425:Chemokine CCL27 / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology; D006801:Humans; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000628:therapy*
D000970:Antineoplastic Agents; C492276:CCL27 protein, human; D054425:Chemokine CCL27; D009842:Oligopeptides; D018664:Interleukin-12; C047981:arginyl-glycyl-aspartic acid