Structure and Cancer Immunotherapy of the B7 Family Member B7x
B7x (B7-H4 or B7S1) is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but it is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest tha...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714008365 |
| _version_ | 1818874060641140736 |
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| author | Hyungjun Jeon Vladimir Vigdorovich Sarah C. Garrett-Thomson Murali Janakiram Udupi A. Ramagopal Yael M. Abadi Jun Sik Lee Lisa Scandiuzzi Kim C. Ohaegbulam Jordan M. Chinai Ruihua Zhao Yu Yao Ying Mao Joseph A. Sparano Steven C. Almo Xingxing Zang |
| author_facet | Hyungjun Jeon Vladimir Vigdorovich Sarah C. Garrett-Thomson Murali Janakiram Udupi A. Ramagopal Yael M. Abadi Jun Sik Lee Lisa Scandiuzzi Kim C. Ohaegbulam Jordan M. Chinai Ruihua Zhao Yu Yao Ying Mao Joseph A. Sparano Steven C. Almo Xingxing Zang |
| author_sort | Hyungjun Jeon |
| collection | DOAJ |
| description | B7x (B7-H4 or B7S1) is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but it is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest that it may be a potent immunosuppressive pathway in human cancers. Here, we determined the crystal structure of the human B7x immunoglobulin variable (IgV) domain at 1.59 Å resolution and mapped the epitopes recognized by monoclonal antibodies. We developed an in vivo system to screen therapeutic monoclonal antibodies against B7x and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor rechallenge. Our data suggest that targeting B7x on tumors is a promising cancer immunotherapy and humanized 1H3 may be efficacious for immunotherapy of human cancers. |
| first_indexed | 2024-12-19T13:04:36Z |
| format | Article |
| id | doaj.art-2e6a6daa6cf14cbca114e32921f5a907 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-19T13:04:36Z |
| publishDate | 2014-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2e6a6daa6cf14cbca114e32921f5a9072022-12-21T20:20:06ZengElsevierCell Reports2211-12472014-11-01931089109810.1016/j.celrep.2014.09.053Structure and Cancer Immunotherapy of the B7 Family Member B7xHyungjun Jeon0Vladimir Vigdorovich1Sarah C. Garrett-Thomson2Murali Janakiram3Udupi A. Ramagopal4Yael M. Abadi5Jun Sik Lee6Lisa Scandiuzzi7Kim C. Ohaegbulam8Jordan M. Chinai9Ruihua Zhao10Yu Yao11Ying Mao12Joseph A. Sparano13Steven C. Almo14Xingxing Zang15Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Biochemistry, Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USADepartment of Biochemistry, Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USADepartment of Biochemistry, Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USAB7x (B7-H4 or B7S1) is a member of the B7 family that can inhibit T cell function. B7x protein is absent in most normal human tissues and immune cells, but it is overexpressed in human cancers and often correlates with negative clinical outcome. The expression pattern and function of B7x suggest that it may be a potent immunosuppressive pathway in human cancers. Here, we determined the crystal structure of the human B7x immunoglobulin variable (IgV) domain at 1.59 Å resolution and mapped the epitopes recognized by monoclonal antibodies. We developed an in vivo system to screen therapeutic monoclonal antibodies against B7x and found that the clone 1H3 significantly inhibited growth of B7x-expressing tumors in vivo via multiple mechanisms. Furthermore, the surviving mice given 1H3 treatment were resistant to tumor rechallenge. Our data suggest that targeting B7x on tumors is a promising cancer immunotherapy and humanized 1H3 may be efficacious for immunotherapy of human cancers.http://www.sciencedirect.com/science/article/pii/S2211124714008365 |
| spellingShingle | Hyungjun Jeon Vladimir Vigdorovich Sarah C. Garrett-Thomson Murali Janakiram Udupi A. Ramagopal Yael M. Abadi Jun Sik Lee Lisa Scandiuzzi Kim C. Ohaegbulam Jordan M. Chinai Ruihua Zhao Yu Yao Ying Mao Joseph A. Sparano Steven C. Almo Xingxing Zang Structure and Cancer Immunotherapy of the B7 Family Member B7x Cell Reports |
| title | Structure and Cancer Immunotherapy of the B7 Family Member B7x |
| title_full | Structure and Cancer Immunotherapy of the B7 Family Member B7x |
| title_fullStr | Structure and Cancer Immunotherapy of the B7 Family Member B7x |
| title_full_unstemmed | Structure and Cancer Immunotherapy of the B7 Family Member B7x |
| title_short | Structure and Cancer Immunotherapy of the B7 Family Member B7x |
| title_sort | structure and cancer immunotherapy of the b7 family member b7x |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714008365 |
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