Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells.
Muc1 is one of the most studied tumor antigens. However, antibodies or antibody-toxin conjugates against Muc1 have not shown significant efficacy for tumors with Muc1 overexpression. In this study, we employed bispecific antibody approach to target Muc1 positive tumor cells. A novel bispecific antib...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5777659?pdf=render |
| _version_ | 1819266432409534464 |
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| author | Yumei Li Changhua Zhou Jing Li Jiayu Liu Limin Lin Li Li Donglin Cao Qing Li Zhong Wang |
| author_facet | Yumei Li Changhua Zhou Jing Li Jiayu Liu Limin Lin Li Li Donglin Cao Qing Li Zhong Wang |
| author_sort | Yumei Li |
| collection | DOAJ |
| description | Muc1 is one of the most studied tumor antigens. However, antibodies or antibody-toxin conjugates against Muc1 have not shown significant efficacy for tumors with Muc1 overexpression. In this study, we employed bispecific antibody approach to target Muc1 positive tumor cells. A novel bispecific antibody, Muc1-Bi-1, was constructed by linking single domain antibodies, anti-Muc1-VHH and anti-CD16-VHH. Muc1-Bi-2, the humanized form of Muc1-Bi-1, was also constructed by grafting. Both Muc1-Bi bispecific antibodies can be efficiently expressed and purified from bacteria. In vitro, the Muc1-Bi bispecific antibodies can recruit Natural Killer (NK) cells to drive potent and specific cell killing of Muc1-overexpressing tumor cells. In xenograft model, the Muc1-Bi bispecific antibodies can suppress tumor growth in the presence of human peripheral blood mononuclear cells (PBMC). These data suggested that the single domain based Muc1-Bi may provide a valid strategy for targeting tumors with Muc1 overexpression. |
| first_indexed | 2024-12-23T21:01:11Z |
| format | Article |
| id | doaj.art-c3de43a8523d4de49bc3d11b7780a5d0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T21:01:11Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c3de43a8523d4de49bc3d11b7780a5d02022-12-21T17:31:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01131e019102410.1371/journal.pone.0191024Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells.Yumei LiChanghua ZhouJing LiJiayu LiuLimin LinLi LiDonglin CaoQing LiZhong WangMuc1 is one of the most studied tumor antigens. However, antibodies or antibody-toxin conjugates against Muc1 have not shown significant efficacy for tumors with Muc1 overexpression. In this study, we employed bispecific antibody approach to target Muc1 positive tumor cells. A novel bispecific antibody, Muc1-Bi-1, was constructed by linking single domain antibodies, anti-Muc1-VHH and anti-CD16-VHH. Muc1-Bi-2, the humanized form of Muc1-Bi-1, was also constructed by grafting. Both Muc1-Bi bispecific antibodies can be efficiently expressed and purified from bacteria. In vitro, the Muc1-Bi bispecific antibodies can recruit Natural Killer (NK) cells to drive potent and specific cell killing of Muc1-overexpressing tumor cells. In xenograft model, the Muc1-Bi bispecific antibodies can suppress tumor growth in the presence of human peripheral blood mononuclear cells (PBMC). These data suggested that the single domain based Muc1-Bi may provide a valid strategy for targeting tumors with Muc1 overexpression.http://europepmc.org/articles/PMC5777659?pdf=render |
| spellingShingle | Yumei Li Changhua Zhou Jing Li Jiayu Liu Limin Lin Li Li Donglin Cao Qing Li Zhong Wang Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells. PLoS ONE |
| title | Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells. |
| title_full | Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells. |
| title_fullStr | Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells. |
| title_full_unstemmed | Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells. |
| title_short | Single domain based bispecific antibody, Muc1-Bi-1, and its humanized form, Muc1-Bi-2, induce potent cancer cell killing in muc1 positive tumor cells. |
| title_sort | single domain based bispecific antibody muc1 bi 1 and its humanized form muc1 bi 2 induce potent cancer cell killing in muc1 positive tumor cells |
| url | http://europepmc.org/articles/PMC5777659?pdf=render |
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