HER2 as a promising target for cytotoxicity T cells in human melanoma therapy.
Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a tar...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3754977?pdf=render |
| _version_ | 1818275804263481344 |
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| author | Juan Ma Huamin Han Deruo Liu Wei Li Hongxiang Feng Xin Xue Xiaoran Wu Ge Niu Ge Zhang Yunfeng Zhao Changzhen Liu Hua Tao Bin Gao |
| author_facet | Juan Ma Huamin Han Deruo Liu Wei Li Hongxiang Feng Xin Xue Xiaoran Wu Ge Niu Ge Zhang Yunfeng Zhao Changzhen Liu Hua Tao Bin Gao |
| author_sort | Juan Ma |
| collection | DOAJ |
| description | Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future. |
| first_indexed | 2024-12-12T22:35:34Z |
| format | Article |
| id | doaj.art-ac5577cb7b434a41985899dbb32e998d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T22:35:34Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ac5577cb7b434a41985899dbb32e998d2022-12-22T00:09:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7326110.1371/journal.pone.0073261HER2 as a promising target for cytotoxicity T cells in human melanoma therapy.Juan MaHuamin HanDeruo LiuWei LiHongxiang FengXin XueXiaoran WuGe NiuGe ZhangYunfeng ZhaoChangzhen LiuHua TaoBin GaoAnti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future.http://europepmc.org/articles/PMC3754977?pdf=render |
| spellingShingle | Juan Ma Huamin Han Deruo Liu Wei Li Hongxiang Feng Xin Xue Xiaoran Wu Ge Niu Ge Zhang Yunfeng Zhao Changzhen Liu Hua Tao Bin Gao HER2 as a promising target for cytotoxicity T cells in human melanoma therapy. PLoS ONE |
| title | HER2 as a promising target for cytotoxicity T cells in human melanoma therapy. |
| title_full | HER2 as a promising target for cytotoxicity T cells in human melanoma therapy. |
| title_fullStr | HER2 as a promising target for cytotoxicity T cells in human melanoma therapy. |
| title_full_unstemmed | HER2 as a promising target for cytotoxicity T cells in human melanoma therapy. |
| title_short | HER2 as a promising target for cytotoxicity T cells in human melanoma therapy. |
| title_sort | her2 as a promising target for cytotoxicity t cells in human melanoma therapy |
| url | http://europepmc.org/articles/PMC3754977?pdf=render |
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