A novel monoclonal antibody KMP1 has potential antitumor activity of bladder cancer by blocking CD44 in vivo and in vitro.

Yujin Chen,Ning Li,Chong Li,Mingxia Ding,Haifeng Wang,Yigang Zuo

doi:10.1002/cam4.1446

Abstract

Bladder cancer becomes a serious medical and social concern due to its high recurrence and mortality rates. Thus, it is urgent to search a novel prognostic biomarker and targeted therapy with high sensitivity and specificity. In this study, we used the human bladder cancer cell line EJ as an immunogen to generate a novel mouse monoclonal antibody KMP1 that specifically bound to bladder cancer, and then, the antitumor effect of KMP1 against bladder cancer was investigated both in vivo and in vitro. The results showed that expression of the KMP1 epitope is consistent with clinical severity and prognosis of bladder cancer. Furthermore, KMP1 not only significantly inhibited the proliferation, migration, and adhesion of EJ cells in vivo, but also suppressed the xenograft tumor growth in nude mice compared with the control group treated with mIgG. Subsequently, the underlying mechanism of KMP1 against bladder cancer was explored via antigen affinity chromatography and mass spectrometry. CD44 located on the cytomembrane was found as the antigen of KMP1. Using RNA interference technology to knock down CD44 expression, we further identified that KMP1 has the antitumor activity by binding to CD44 and blocking its functions. In conclusion, KMP1 might be valuable for development as a promising specific diagnostic biomarker or targeted agent for bladder cancer.

Highlights

Bladder cancer is one of the most common urogenital malignant tumors with frequent recurrence and poor prognosis, which make it become one of the main causes of death in the world
These results indicate that KMP1 could recognize antigen located on the cytomembrane in bladder cancer
Standard bladder cancer treatment guidelines include tumor resection complemented by cisplatin-based chemotherapy or immunotherapy

Summary

Introduction

Bladder cancer is one of the most common urogenital malignant tumors with frequent recurrence and poor prognosis, which make it become one of the main causes of death in the world. The incidence and death rates of bladder cancer are rising year by year. It was estimated there were 429,800 new cases and 165,100 deaths worldwide in 2012 [1] and 79,030 new cases and 16,870 deaths in the United States in 2017 [2]. About 70% of patients with bladder cancer are non– muscle-invasive bladder cancer (NMIBC) with a tendency of recurrence and 30% are muscle-invasive bladder cancer (MIBC) associated with a high risk of death from distant metastases [4]. Patients with NMIBC were treated with tumor removal via the transurethral approach followed by a postoperative immediate intravesical instillation of chemotherapy or immunotherapy, while patients with MIBC were treated with radical cystectomy and perioperative

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Results

Conclusion