B7-H3 Targeted Antibody-based Immunotherapy of Malignant Diseases

Overview

Journal Expert Opin Biol Ther

Specialties Biology
Pharmacology

Date 2020 Dec 10

PMID 33301369

Citations 17

Authors

Theodoros Michelakos

Filippos Kontos

Omar Barakat

Luke Maggs

Joseph H Schwab

Cristina R Ferrone

Soldano Ferrone

Affiliations

Soon will be listed here.

Abstract

: Recent advances in immuno-oncology and bioengineering have rekindled the interest in monoclonal antibody (mAb)-based immunotherapies for malignancies. Crucial for their success is the identification of tumor antigens (TAs) that can serve as targets. B7-H3, a member of the B7 ligand family, represents such a TA. Although its exact functions and receptor(s) remain unclear, B7-H3 has predominantly a pro-tumorigenic effect mainly by suppressing the anti-tumor functions of T-cells.: Initially we present a historical perspective on TA-specific antibodies for diagnosis and treatment of malignancies. Following a description of the TA requirements to be an attractive antibody-based immunotherapy target, we show that B7-H3 fulfills these criteria. We discuss its structure and functions. In a review and pooled analysis, we describe the limited B7-H3 expression in normal tissues and estimate B7-H3 expression frequency in tumors, tumor-associated vasculature and cancer initiating cells (CICs). Lastly, we discuss the association of B7-H3 expression in tumors with poor prognosis.: B7-H3 is an attractive target for mAb-based cancer immunotherapy. B7-H3-targeting strategies are expected to be highly effective and - importantly - safe. To fully exploit the diagnostic and therapeutic potential of B7-H3, its expression in pre-malignant lesions, serum, metastases, and CICs requires further investigation.

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References

Chapoval A, Ni J, Lau J, Wilcox R, Flies D, Liu D . B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol. 2001; 2(3):269-74. DOI: 10.1038/85339. View

Xylinas E, Robinson B, Kluth L, Volkmer B, Hautmann R, Kufer R . Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder. Eur J Surg Oncol. 2013; 40(1):121-7. DOI: 10.1016/j.ejso.2013.08.023. View

Brustmann H, Igaz M, Eder C, Brunner A . Epithelial and tumor-associated endothelial expression of B7-H3 in cervical carcinoma: relation with CD8+ intraepithelial lymphocytes, FIGO stage, and phosphohistone H3 (PHH3) reactivity. Int J Gynecol Pathol. 2015; 34(2):187-95. DOI: 10.1097/PGP.0000000000000116. View

Bin Z, Guangbo Z, Yan G, Huan Z, Desheng L, Xueguang Z . Overexpression of B7-H3 in CD133+ colorectal cancer cells is associated with cancer progression and survival in human patients. J Surg Res. 2014; 188(2):396-403. DOI: 10.1016/j.jss.2014.01.014. View

Zhan S, Liu Z, Zhang M, Guo T, Quan Q, Huang L . Overexpression of B7-H3 in α-SMA-Positive Fibroblasts Is Associated With Cancer Progression and Survival in Gastric Adenocarcinomas. Front Oncol. 2020; 9:1466. PMC: 6966326. DOI: 10.3389/fonc.2019.01466. View

Martinez M, Moon E . CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment. Front Immunol. 2019; 10:128. PMC: 6370640. DOI: 10.3389/fimmu.2019.00128. View

Zang X, Sullivan P, Soslow R, Waitz R, Reuter V, Wilton A . Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas. Mod Pathol. 2010; 23(8):1104-12. PMC: 2976590. DOI: 10.1038/modpathol.2010.95. View

Quandt D, Fiedler E, Boettcher D, Marsch W, Seliger B . B7-h4 expression in human melanoma: its association with patients' survival and antitumor immune response. Clin Cancer Res. 2011; 17(10):3100-11. DOI: 10.1158/1078-0432.CCR-10-2268. View

Ingebrigtsen V, Boye K, Nesland J, Nesbakken A, Flatmark K, Fodstad O . B7-H3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome. BMC Cancer. 2014; 14:602. PMC: 4148536. DOI: 10.1186/1471-2407-14-602. View

10.

Kraan J, Van Den Broek P, Verhoef C, Grunhagen D, Taal W, Gratama J . Endothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells. Br J Cancer. 2014; 111(1):149-56. PMC: 4090744. DOI: 10.1038/bjc.2014.286. View

11.

Kim G, Kim N, Park M, Lee J . B7-H3 and B7-H4 expression in phyllodes tumors of the breast detected by RNA in situ hybridization and immunohistochemistry: Association with clinicopathological features and T-cell infiltration. Tumour Biol. 2018; 40(11):1010428318815032. DOI: 10.1177/1010428318815032. View

12.

Parra E, Villalobos P, Zhang J, Behrens C, Mino B, Swisher S . Immunohistochemical and Image Analysis-Based Study Shows That Several Immune Checkpoints are Co-expressed in Non-Small Cell Lung Carcinoma Tumors. J Thorac Oncol. 2018; 13(6):779-791. DOI: 10.1016/j.jtho.2018.03.002. View

13.

Maeda N, Yoshimura K, Yamamoto S, Kuramasu A, Inoue M, Suzuki N . Expression of B7-H3, a potential factor of tumor immune evasion in combination with the number of regulatory T cells, affects against recurrence-free survival in breast cancer patients. Ann Surg Oncol. 2014; 21 Suppl 4:S546-54. PMC: 4236607. DOI: 10.1245/s10434-014-3564-2. View

14.

Yuan H, Wei X, Zhang G, Li C, Zhang X, Hou J . B7-H3 over expression in prostate cancer promotes tumor cell progression. J Urol. 2011; 186(3):1093-9. DOI: 10.1016/j.juro.2011.04.103. View

15.

Arigami T, Uenosono Y, Hirata M, Yanagita S, Ishigami S, Natsugoe S . B7-H3 expression in gastric cancer: a novel molecular blood marker for detecting circulating tumor cells. Cancer Sci. 2011; 102(5):1019-24. DOI: 10.1111/j.1349-7006.2011.01877.x. View

16.

Wu J, Wang F, Liu X, Zhang T, Liu F, Ge X . Correlation of IDH1 and B7H3 expression with prognosis of CRC patients. Eur J Surg Oncol. 2018; 44(8):1254-1260. DOI: 10.1016/j.ejso.2018.05.005. View

17.

Kohler G, Milstein C . Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975; 256(5517):495-7. DOI: 10.1038/256495a0. View

18.

Sun X, Yu Y, Ma L, Xue X, Gao Z, Ma J . T cell cytotoxicity toward hematologic malignancy via B7-H3 targeting. Invest New Drugs. 2019; 38(3):722-732. DOI: 10.1007/s10637-019-00819-y. View

19.

Sun M, Richards S, Prasad D, Mai X, Rudensky A, Dong C . Characterization of mouse and human B7-H3 genes. J Immunol. 2002; 168(12):6294-7. DOI: 10.4049/jimmunol.168.12.6294. View

20.

Cai D, Li J, Liu D, Hong S, Qiao Q, Sun Q . Tumor-expressed B7-H3 mediates the inhibition of antitumor T-cell functions in ovarian cancer insensitive to PD-1 blockade therapy. Cell Mol Immunol. 2019; 17(3):227-236. PMC: 7051965. DOI: 10.1038/s41423-019-0305-2. View