Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth
Background Small cell lung cancer (SCLC) accounts for 15% of lung cancers, and the primary treatment of this malignancy is chemotherapy and radiotherapy. Delta-like 3 (DLL3) is an attractive target for SCLC immunotherapy since its expression is highly restricted to SCLC with a neglectable appearance...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2020-05-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/8/1/e000785.full |
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| _version_ | 1846172698122649600 |
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| author | Xin Chen Norhan Amar Yuankui Zhu Chunguang Wang Chunjiao Xia Xiaoqing Yang Dongde Wu Mingqian Feng |
| author_facet | Xin Chen Norhan Amar Yuankui Zhu Chunguang Wang Chunjiao Xia Xiaoqing Yang Dongde Wu Mingqian Feng |
| author_sort | Xin Chen |
| collection | DOAJ |
| description | Background Small cell lung cancer (SCLC) accounts for 15% of lung cancers, and the primary treatment of this malignancy is chemotherapy and radiotherapy. Delta-like 3 (DLL3) is an attractive target for SCLC immunotherapy since its expression is highly restricted to SCLC with a neglectable appearance on normal adult tissues. In the current study, we aimed to explore the efficacy of DLL3-targeted SCLC immunotherapy via the engagement of T cell.Methods As a proof of concept, we constructed DLL3-targeted bispecific antibody and chimeric antigen receptor (CAR)-modified T cells. In vitro and in vivo tumor-suppression activity of these treatments alone or in combination with a Program Death-1 (PD-1) inhibitory antibody was evaluated.Results In vitro studies showed that both DLL3 bispecific antibody and CAR-T efficiently killed DLL3-positive cancer cells, including the native SCLC cell lines H446, H196, H82, and the artificial A431 cells that were forcefully overexpressing DLL3. In vivo studies in xenograft mouse models demonstrated that both bispecific antibody and CAR-T suppressed the tumor growth, and combination therapy with PD-1 inhibitory antibody dramatically improved the efficacy of the DLL3 bispecific antibody, but not the CAR-T cells.Conclusions Our results demonstrated that DLL3-targeted bispecific antibody plus PD-1 inhibition was effective in controlling SCLC growth. |
| format | Article |
| id | doaj-art-d1986f55e7ff4a8fb8f10faf82214fd0 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-d1986f55e7ff4a8fb8f10faf82214fd02024-11-09T11:45:07ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2020-000785Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growthXin Chen0Norhan Amar1Yuankui Zhu2Chunguang Wang3Chunjiao Xia4Xiaoqing Yang5Dongde Wu6Mingqian Feng7State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China1 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China1 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China2 Department of Thoracic Surgery, Jilin University Second Hospital, Changchun, Jilin, China1 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China3 Hospital of Huazhong Agricultural University, Huazhong Agricultural University, Wuhan, Hubei, China4 Department of Hepatobiliary and Pancreatic Surgery, Hubei Cancer Hospital, Wuhan, Hubei, China1 College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, ChinaBackground Small cell lung cancer (SCLC) accounts for 15% of lung cancers, and the primary treatment of this malignancy is chemotherapy and radiotherapy. Delta-like 3 (DLL3) is an attractive target for SCLC immunotherapy since its expression is highly restricted to SCLC with a neglectable appearance on normal adult tissues. In the current study, we aimed to explore the efficacy of DLL3-targeted SCLC immunotherapy via the engagement of T cell.Methods As a proof of concept, we constructed DLL3-targeted bispecific antibody and chimeric antigen receptor (CAR)-modified T cells. In vitro and in vivo tumor-suppression activity of these treatments alone or in combination with a Program Death-1 (PD-1) inhibitory antibody was evaluated.Results In vitro studies showed that both DLL3 bispecific antibody and CAR-T efficiently killed DLL3-positive cancer cells, including the native SCLC cell lines H446, H196, H82, and the artificial A431 cells that were forcefully overexpressing DLL3. In vivo studies in xenograft mouse models demonstrated that both bispecific antibody and CAR-T suppressed the tumor growth, and combination therapy with PD-1 inhibitory antibody dramatically improved the efficacy of the DLL3 bispecific antibody, but not the CAR-T cells.Conclusions Our results demonstrated that DLL3-targeted bispecific antibody plus PD-1 inhibition was effective in controlling SCLC growth.https://jitc.bmj.com/content/8/1/e000785.full |
| spellingShingle | Xin Chen Norhan Amar Yuankui Zhu Chunguang Wang Chunjiao Xia Xiaoqing Yang Dongde Wu Mingqian Feng Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth Journal for ImmunoTherapy of Cancer |
| title | Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth |
| title_full | Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth |
| title_fullStr | Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth |
| title_full_unstemmed | Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth |
| title_short | Combined DLL3-targeted bispecific antibody with PD-1 inhibition is efficient to suppress small cell lung cancer growth |
| title_sort | combined dll3 targeted bispecific antibody with pd 1 inhibition is efficient to suppress small cell lung cancer growth |
| url | https://jitc.bmj.com/content/8/1/e000785.full |
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