Pritumumab (also known as CLNH11, CLN-IgG, and ACA-11) is a natural human IgG1 kappa antibody that has been derived from a B cell isolated from regional draining lymph node of a cervical carcinoma patient. The recognized antigen is an altered form of vimentin, called ecto-domain vimentin (EDV), that is expressed on the cell surface of epithelial tumor cells. Developed as a lead product by Nascent Biotech, Inc., pritumumab is the first fully human antibody used for the treatment of glioma in clinical trials. In addition, the FDA granted it orphan drug designation in 2015. Pritumumab has already undergone various Phase II clinical trials in Japan. Patients treated with the antibody showed an overall survival rate of 25 to 30 percent after a five-year period, as opposed to the three percent survival rate of standard therapies like surgery, radiation, and chemotherapy. What makes Pritumumab unique as a monoclonal antibody therapy is its ability to penetrate the blood-brain barrier due to its high isoelectric point. Hence, the treatment of brain tumors is its primary indication, although the target antigen of the antibody cannot only be found in brain cancer, but in pancreatic, renal cell, and breast cancers as well. Furthermore, Pritumumab toxicities have been minimal, suggesting that the cure is safe and effective for brain cancer patients. There is even histological staining evidence that shows that Pritumumab could be highly useful in treating additional cancer types.
The histological feature in the tumor tissue shows there are a variety of heterogenous shaped cells including those cells with abnormal nuclear membrane architecture. This indicates that the tumor is the mixture of a variety of differentiated tumor cells and tumor stem cells in T-niche. The dominant phenomenon in malignancy is EMT/MET. This mechanism leaves tumor stem cell open to grow at any site in the host. In the histology of the tumor site there are many irregular shaped cells that seem to grow with mortality (blastogenesis). These T-niche cells are mostly vimentin positive cells, and some are committed to apoptosis. a cellular re-programming process in which the epithelial cells acquire a mesenchymal phenotype that renders the cells to dramatically alter their shape and exhibit increased motility. This EMT is characterized by the expression of vimentin IFs in epithelial cells, which normally express only keratin IFs. Accordingly, during the reverse process of EMT, known as mesenchymal-epithelial transition (MET), the cells start acquiring epithelial phenotype and show a decreased vimentin expression with lower motility rates. Increased vimentin expression has been reported in various tumor cell lines and tissues including prostate cancer, breast cancer, endometrial cancer, CNS tumors, malignant melanoma and gastrointestinal tumors including pancreatic, colorectal and hepatic cancers. Pritumumab is a natural human IgG1 kappa antibody which could recognize the altered form of vimentin. The drug induces tumor cell death by Antibody-dependent cell-mediated cytotoxicity (ADCC). It could penetrate the blood-brain barrier due to its high isoelectric point. Therefore, pritumumab is suitable for development as an anti-tumor therapeutic.
Fig 1. Mechanism of Action of Pritumumab