Development of a fully human anti‐GITR antibody with potent antitumor activity using H2L2 mice
Glucocorticoid‐induced TNF receptor‐related (GITR) can act as a co‐stimulatory receptor, representing a potential target for safely enhancing immunotherapy efficacy. GITR is triggered by a GITR ligand or an agonist antibody and activates CD8+ and CD4+ effector T cells, reducing tumor‐infiltrating Tr...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-08-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13451 |
| _version_ | 1818179074759065600 |
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| author | Qiuli Tong Hu Liu Qianqian Qi Chaohui Dai Teddy Yang Feng Qian |
| author_facet | Qiuli Tong Hu Liu Qianqian Qi Chaohui Dai Teddy Yang Feng Qian |
| author_sort | Qiuli Tong |
| collection | DOAJ |
| description | Glucocorticoid‐induced TNF receptor‐related (GITR) can act as a co‐stimulatory receptor, representing a potential target for safely enhancing immunotherapy efficacy. GITR is triggered by a GITR ligand or an agonist antibody and activates CD8+ and CD4+ effector T cells, reducing tumor‐infiltrating Treg numbers and resulting in activation of immune responses and tumor cell destruction by effector T cells. GITR is an attractive target for immunotherapy, especially in combination therapy with immune checkpoint inhibitors, as is being explored in clinical trials. Using H2L2 transgenic mice encoding the human immunoglobulin variable region and hybridoma technology, we generated a panel of fully human antibodies that showed excellent specific affinity and strong activation of human T cells. After conversion to fully human antibodies and engineering modification, we obtained an anti‐GITR antibody hab019e2 with enhanced antitumor activity in a B‐hGITR MC38 mouse model compared to Tab9H6V3, an anti‐GITR antibody that activates T cells and inhibits Treg suppression from XenoMouse. As a fully human antibody with its posttranslational modification hot spot removed, the hab019e2 antibody exerted more potent therapeutic effects, and may have potential as a novel and developable antibody targeting GITR for follow‐up drug studies. |
| first_indexed | 2024-12-11T20:58:06Z |
| format | Article |
| id | doaj.art-18c31dff14264b6bb4e923947ba750a3 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-11T20:58:06Z |
| publishDate | 2022-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-18c31dff14264b6bb4e923947ba750a32022-12-22T00:51:04ZengWileyFEBS Open Bio2211-54632022-08-011281542155710.1002/2211-5463.13451Development of a fully human anti‐GITR antibody with potent antitumor activity using H2L2 miceQiuli Tong0Hu Liu1Qianqian Qi2Chaohui Dai3Teddy Yang4Feng Qian5Shanghai Public Health Clinical Center, Human Phenome Institute and School of Life Sciences Fudan University Shanghai ChinaShanghai Chempartner Co., Ltd ChinaShanghai Chempartner Co., Ltd ChinaShanghai PharmaExplorer Co., Ltd. ChinaShanghai Chempartner Co., Ltd ChinaShanghai Public Health Clinical Center, Human Phenome Institute and School of Life Sciences Fudan University Shanghai ChinaGlucocorticoid‐induced TNF receptor‐related (GITR) can act as a co‐stimulatory receptor, representing a potential target for safely enhancing immunotherapy efficacy. GITR is triggered by a GITR ligand or an agonist antibody and activates CD8+ and CD4+ effector T cells, reducing tumor‐infiltrating Treg numbers and resulting in activation of immune responses and tumor cell destruction by effector T cells. GITR is an attractive target for immunotherapy, especially in combination therapy with immune checkpoint inhibitors, as is being explored in clinical trials. Using H2L2 transgenic mice encoding the human immunoglobulin variable region and hybridoma technology, we generated a panel of fully human antibodies that showed excellent specific affinity and strong activation of human T cells. After conversion to fully human antibodies and engineering modification, we obtained an anti‐GITR antibody hab019e2 with enhanced antitumor activity in a B‐hGITR MC38 mouse model compared to Tab9H6V3, an anti‐GITR antibody that activates T cells and inhibits Treg suppression from XenoMouse. As a fully human antibody with its posttranslational modification hot spot removed, the hab019e2 antibody exerted more potent therapeutic effects, and may have potential as a novel and developable antibody targeting GITR for follow‐up drug studies.https://doi.org/10.1002/2211-5463.13451engineering modificationfully human antibodyGITRH2L2 miceimmunization strategiesT cell |
| spellingShingle | Qiuli Tong Hu Liu Qianqian Qi Chaohui Dai Teddy Yang Feng Qian Development of a fully human anti‐GITR antibody with potent antitumor activity using H2L2 mice FEBS Open Bio engineering modification fully human antibody GITR H2L2 mice immunization strategies T cell |
| title | Development of a fully human anti‐GITR antibody with potent antitumor activity using H2L2 mice |
| title_full | Development of a fully human anti‐GITR antibody with potent antitumor activity using H2L2 mice |
| title_fullStr | Development of a fully human anti‐GITR antibody with potent antitumor activity using H2L2 mice |
| title_full_unstemmed | Development of a fully human anti‐GITR antibody with potent antitumor activity using H2L2 mice |
| title_short | Development of a fully human anti‐GITR antibody with potent antitumor activity using H2L2 mice |
| title_sort | development of a fully human anti gitr antibody with potent antitumor activity using h2l2 mice |
| topic | engineering modification fully human antibody GITR H2L2 mice immunization strategies T cell |
| url | https://doi.org/10.1002/2211-5463.13451 |
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