Anatumomab mafenatox, also known as ABR-214936, is an antineoplastic developed by Active Biotech. It is a recombinant fusion protein composed of Fab fragment of monoclonal antibody targeting TAG-72 and enterotoxin ('mafenatox') of Staphylococcus aureus. Staphylococcus aureus enterotoxin A is a superantigen with certain antitumor activity. Anatumomab mafenatox has been investigated in the treatment of non-small cell lung cancer, pancreatic cancer and renal cancer. In 2003, scientists conducted a phase II study of anatumomab mafenatox in the treatment of advanced non-small cell lung cancer. After that, it has been reported that anatumomab mafenatox is used in the non-controlled phase II clinical study of advanced pancreatic cancer, and the results show that ABR214936 is a promising active drug for the treatment of this refractory cancer. However, phase I and phase II trials of anatumomab mafenatox in non-small cell lung cancer were discontinued in Europe and the United States in 2004, respectively. In the same year, the second phase of anatumomab mafenatox in the treatment of pancreatic cancer was discontinued in the United Kingdom. Since then, there has been less research on anatumomab mafenatox in cancer treatment.
The principle of anatumomab mafenatox in the treatment of tumor is mainly based on tumor-targeted superantigen. Superantigens refer to a class of retrovirus proteins and bacterial exotoxins that bind directly to MHC and T cells of antigen-presenting cells and activate T cells without antigen-presenting cells. When such antigens exist in trace amounts, a large number of T cells can be activated. It has been found that superantigen can produce superantigen-dependent cytotoxicity on MHC-Ⅱ+ tumor, and at the same time produce a large number of cytokines, thus mediating the anti-tumor effect. Anatumomab mafenatox plays an anti-tumor role through targeting tumor-associated glycoprotein 72 (TAG-72). TAG-72 is a glycoprotein found on the surface of tumor cells with a molecular weight of more than 1000 KD. It has been found on the surface of a variety of tumor cells, including ovarian cancer, breast cancer, colon cancer, lung cancer and pancreatic cancer. Studies have found that TAG-72 is highly expressed in most malignant cancer tumors, so it is also considered as a tumor marker. Immunoradiometric assay for TAG-72 can distinguish benign from malignant diseases, which provides a basis for the detection and diagnosis of cancer. The mechanism of anatumomab mafenatox is to kill tumor cells and mediate anti-tumor effect through antibody-mediated cytotoxicity and tumor superantigen.
Fig.1 Mechanism of action of Anatumomab mafenatox