Treating Bladder Cancer: Engineering of Current and Next Generation Antibody-, Fusion Protein-, mRNA-, Cell- and Viral-Based Therapeutics

Abstract

Bladder cancer is a frequent malignancy and has a clinical need for new therapeutic approaches. Antibody and protein technologies came a long way in recent years and new engineering approaches were applied to generate innovative therapeutic entities with novel mechanisms of action. Furthermore, mRNA-based pharmaceuticals recently reached the market and CAR-T cells and viral-based gene therapy remain a major focus of biomedical research. This review focuses on the engineering of biologics, particularly therapeutic antibodies and their application in preclinical development and clinical trials, as well as approved monoclonal antibodies for the treatment of bladder cancer. Besides, newly emerging entities in the realm of bladder cancer like mRNA, gene therapy or cell-based therapeutics are discussed and evaluated. As many discussed molecules exhibit unique mechanisms of action based on innovative protein engineering, they reflect the next generation of cancer drugs. This review will shed light on the engineering strategies applied to develop these next generation treatments and provides deeper insights into their preclinical profiles, clinical stages, and ongoing trials. Furthermore, the distribution and expression of the targeted antigens and the intended mechanisms of action are elucidated.

A Generic Strategy to Generate Bifunctional Two-in-One Antibodies by Chicken Immunization

“…Overexpression of PD-L1 is observed in a variety of malignancies and represents a mechanism by which cancer evades immune surveillance ( 24 , 26 ). EGFR, which is natively expressed on epithelial cells in the skin and lung, is overexpressed in a wide range of cancers including bladder cancer, lung cancer, colorectal cancer, and breast cancer, where it is involved in tumor progression and metastasis ( 25 , 27 – 29 ). Koopmans and coworkers demonstrated that tumor-specificity can be increased by EGFR directed PD-L1 blockade, resulting in a potentially favorable safety profile of the described bsAb ( 30 ).…”

BK and JC polyomaviruses and risk of urothelial bladder carcinoma: a preliminary study in the northern shores of Persian Gulf, Iran

“…Bladder cancer is the 9th leading cause of cancer-related deaths worldwide, causing nearly 210.000 deaths each year [ 1 ]. Among possible risk factors for bladder cancer, infectious pathogens are of particular interest for their carcinogenesis properties.…”

“…All patients and the legal guardians of the deceased persons gave written informed consent to use their samples for viral detection and analysis. Grading and staging of tumors were carried out according to the World Health Organization/International Society of Urological Pathology (WHO/ISUP) and the American Joint Committee on Cancer/tumor, nodes, metastases (AJCC/TNM) staging system, respectively [ 1 , 10 , 11 ]. Demographic data and clinicopathologic characteristics were obtained from the medical record of the patients at the pathology department of the hospitals.…”

“…Bladder cancer, with approximately 570,000 new cases and an estimated 210,000 deaths annually, is considered to be the tenth most common cancer worldwide [ 1 ]. Over 90% of bladder cancers are transitional cell carcinoma, which are currently classified as urothelial bladder carcinoma, whereas 5% are squamous cell carcinoma and 2% are adenocarcinoma [ 1 ].…”

“…Bladder cancer, with approximately 570,000 new cases and an estimated 210,000 deaths annually, is considered to be the tenth most common cancer worldwide [ 1 ]. Over 90% of bladder cancers are transitional cell carcinoma, which are currently classified as urothelial bladder carcinoma, whereas 5% are squamous cell carcinoma and 2% are adenocarcinoma [ 1 ]. Cigarette smoking, prolonged use of antineoplastic drugs, arsenic in drinking water, occupational exposure to polycyclic hydrocarbons, aromatic amines and ionizing radiation, genetic background, chronic cystitis, schistosomiasis, and some bacterial and viral infections are possible risk factors for bladder cancer [ 2 , 3 ].…”