ABSTRACT

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

摘要

简介：免疫肿瘤学和生物工程的最新进展重新点燃了人们对基于单克隆抗体 (mAb) 的恶性肿瘤免疫疗法的兴趣。他们成功的关键是鉴定出可以作为靶点的肿瘤抗原（TA）。B7-H3 是 B7 配体家族的成员，代表了这样的 TA。尽管其确切功能和受体尚不清楚，但 B7-H3 主要通过抑制 T 细胞的抗肿瘤功能来发挥促肿瘤作用。

涵盖领域：首先，我们提出了用于诊断和治疗恶性肿瘤的 TA 特异性抗体的历史观点。在描述了成为有吸引力的基于抗体的免疫治疗靶点的 TA 要求后，我们表明 B7-H3 满足这些标准。我们讨论它的结构和功能。在回顾和汇总分析中，我们描述了正常组织中有限的 B7-H3 表达，并估计了肿瘤、肿瘤相关脉管系统和癌症起始细胞 (CIC) 中的 B7-H3 表达频率。最后，我们讨论了肿瘤中 B7-H3 表达与不良预后的关系。

专家意见：B7-H3 是基于 mAb 的癌症免疫疗法的一个有吸引力的靶点。B7-H3 靶向策略预计将非常有效，而且重要的是安全。为了充分利用 B7-H3 的诊断和治疗潜力，其在癌前病变、血清、转移瘤和 CIC 中的表达需要进一步研究。