Antibody-HPR ImmunoRNases Fusion Protein

With advanced technical platforms, Creative Biolabs provides customized antibody-HPR immunoRNases fusion protein services to help your projects. Our professional scientists have extensive experience in antibody production, synthetic chemistry, as well as bio-conjugation, and we are committed to providing high-quality services to promote the development of innovative cancer treatments.

HRP

Antibody-directed toxic enzyme fusion proteins have been widely used in cancer therapy. The enzyme component used in this system is toxic, such as human pancreatic RNase (HPR). Ribonucleases (RNases) of the superfamily A, including HPR (also known as RNase A or RNase 1), eosinophil derived neurotoxin (EDN, RNase 2), eosinophil cationic protein (ECP, RNase 3) and angiogenin (ANG, RNase 5), exhibit potent anti-neoplastic activity and do not mediate appreciable immunogenicity or non-specific toxicity in both animal models and cancer patients. Human RNases possess limited cytotoxicity but greater specificity can be achieved when fused with a disease-specific antibody. Conjugation or fusion of targeted therapeutic RNases (immunoRNases) to tumor specific antibodies is a promising approach for cancer therapy. An immunoRNase is, in fact, an immuno-pro-toxin. High levels of HPR have been implicated as a tumor biomarker of pancreatic adenocarcinomas. Coupling of HPR to a humanized antibody or antibody derivative putatively eliminates the immunogenicity of an immunotoxin.

Fig.1 Structure of HPR.

Antibody-HPR ImmunoRNases Fusion Protein

HPR has been shown to exhibit specific tumor suppression in fusion with a range of disease-specific ligands and antibodies. The concept of using antibody-HPR immunoRNase for cancer treatment was based on initial immunoRNase studies conducted using antibody-bovine pancreatic RNase conjugates in 1999. For instance, immunoRNases, made up of a human anti-ErbB2 scFv and HPR, have been engineered to overcome the limits of other immunotoxins, such as immunogenicity and nonspecific toxicity. Anti-ErbB2 scFv-HPR immunoRNase demonstrated selective cytotoxicity towards carcinomas expressing the ErbB2 receptor. The immunoRNase was finally 16-times more effective at inhibiting ErbB2⁺ tumor cells than the scFv alone. Similar results have been reported in numerous studies.

Fig.2 A ribbon representation of hypothetical models of an immunoRNase. (De, 2009)

The immunoRNase is a promising candidate for the immunotherapy of cancer because of its expected low immunogenicity, good production yields, and potent effector function upon target cell binding and internalization. Equipped with state-of-the-art research and manufacturing facilities, Creative Biolabs is dedicated to helping our clients design and prepare highly customized antibody-HPR immunoRNases fusion protein using our featured services. With novel technique platforms and professional experiment services, we get ready to provide you with the best services. Please feel free to contact us for more details.

Reference

1. De Lorenzo, C.; D’ Alessio, G. Human anti-ErbB2 immunoagents-immunoRNases and compact antibodies. The FEBS journal. 2009, 276(6), 1527-1535.