Theranostics 2020; 10(23):10498-10512. doi:10.7150/thno.49480 This issue Cite

Research Paper

Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy

Cheng Huang1*, Hongjian Li1*, Yunyu Feng1, Xiaoling Li1, Zongliang Zhang1, Caiying Jiang1, Jichao Wang1, Chenli Yang1, Yuying Fu, Min Mu1, Shasha Zhao1, Zeng Wang1, Yi Kuang1, Huan Hou1, Yuelong Wang1,2, Wenhao Guo3, Jianguo Xu2, Hui Yang4, Liangxue Zhou2, Aiping Tong1✉, Gang Guo1✉

1. State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, China.
2. Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, China.
3. Department of Abdominal Oncology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, 610041, China.
4. Department of Otolaryngology, Head and Neck Surgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan province, 610041, China.
*These authors contributed equally to this manuscript.

Citation:
Huang C, Li H, Feng Y, Li X, Zhang Z, Jiang C, Wang J, Yang C, Fu Y, Mu M, Zhao S, Wang Z, Kuang Y, Hou H, Wang Y, Guo W, Xu J, Yang H, Zhou L, Tong A, Guo G. Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy. Theranostics 2020; 10(23):10498-10512. doi:10.7150/thno.49480. https://www.thno.org/v10p10498.htm
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Abstract

Graphic abstract

Rationale: Current traditional treatment options are frequently ineffective to fight against ovarian cancer due to late diagnosis and high recurrence. Therefore, there is a vital need for the development of novel therapeutic agents. B7H3, an immune checkpoint protein, is highly expressed in various cancers, representing it a promising target for cancer immunotherapy. Although targeting B7H3 by bispecific T cell-engaging antibodies (BiTE) has achieved successes in hematological malignancies during recent years, attempts to use them for the treatment of solid cancers are less favorable, in part due to the heterogeneity of tumors. Sorafenib is an unselective inhibitor of multiple kinases currently being tested in clinical trials for several tumors, including ovarian cancer which showed limited activity and inevitable side effect for ovarian cancer treatment. However, it is able to enhance antitumor immune response, which indicates sorafenib may improve the efficiency of immunotherapy.

Methods: We evaluated the expression of B7H3 in ovarian cancer using online database and validated its expression of tumor tissues by immunohistochemistry staining. Then, B7H3 expression and the effects of sorafenib on ovarian cancer cell lines were determined by flow cytometry. In addition, 2D and 3D ovarian cancer models were established to test the combined therapeutic effect in vitro. Finally, the efficiency of B7H3×CD3 BiTE alone and its combination with sorafenib were evaluated both in vitro and in vivo.

Results: Our data showed that B7H3 was highly expressed in ovarian cancer compared with normal samples. Treatment with sorafenib inhibited ovarian cancer cell proliferation and induced a noticeable upregulation of B7H3 expression level. Further study suggested that B7H3×CD3 BiTE was effective in mediating T cell killing to cancer cells. Combined treatment of sorafenib and B7H3×CD3 BiTE had synergistic anti-tumor effects in ovarian cancer models.

Conclusions: Overall, our study indicates that combination therapy with sorafenib and B7H3×CD3 BiTE may be a new therapeutic option for the further study of preclinical treatment of OC.

Keywords: Ovarian cancer, sorafenib, immunotherapy, B7H3, bispecific antibody


Citation styles

APA
Huang, C., Li, H., Feng, Y., Li, X., Zhang, Z., Jiang, C., Wang, J., Yang, C., Fu, Y., Mu, M., Zhao, S., Wang, Z., Kuang, Y., Hou, H., Wang, Y., Guo, W., Xu, J., Yang, H., Zhou, L., Tong, A., Guo, G. (2020). Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy. Theranostics, 10(23), 10498-10512. https://doi.org/10.7150/thno.49480.

ACS
Huang, C.; Li, H.; Feng, Y.; Li, X.; Zhang, Z.; Jiang, C.; Wang, J.; Yang, C.; Fu, Y.; Mu, M.; Zhao, S.; Wang, Z.; Kuang, Y.; Hou, H.; Wang, Y.; Guo, W.; Xu, J.; Yang, H.; Zhou, L.; Tong, A.; Guo, G. Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy. Theranostics 2020, 10 (23), 10498-10512. DOI: 10.7150/thno.49480.

NLM
Huang C, Li H, Feng Y, Li X, Zhang Z, Jiang C, Wang J, Yang C, Fu Y, Mu M, Zhao S, Wang Z, Kuang Y, Hou H, Wang Y, Guo W, Xu J, Yang H, Zhou L, Tong A, Guo G. Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy. Theranostics 2020; 10(23):10498-10512. doi:10.7150/thno.49480. https://www.thno.org/v10p10498.htm

CSE
Huang C, Li H, Feng Y, Li X, Zhang Z, Jiang C, Wang J, Yang C, Fu Y, Mu M, Zhao S, Wang Z, Kuang Y, Hou H, Wang Y, Guo W, Xu J, Yang H, Zhou L, Tong A, Guo G. 2020. Combination therapy with B7H3-redirected bispecific antibody and Sorafenib elicits enhanced synergistic antitumor efficacy. Theranostics. 10(23):10498-10512.

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