The Nature of Mutated Muc5ac, an Oncofetal Protein, Expressed in Colorectal Cancer: It’s Role as a Therapeutic Immunogen

Arlen M, Arlen P, Dubeykovskiy A, Saric O, Coppa G, Conte C and Molmenti E

Department of Surgery, North Shore University Hospital, USA
Department of Surgery Northwell Health System, Hofstra University College of Medicine, USA

^*Correspondance to: Arlen M 

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Abstract:

The present concept of effectively treating a malignant lesion, especially one in the process of metastasis, requires being able to turn on cytotoxic T cells that can recognize and destroy the tumor. All attempts at employing this system using TIL and other T cell populations have failed to date. Prehn in the 1950 s postulated that tumors act in a similar fashion to invading bacteria and viruses. Here the host can recognize the foreign invader by defining immunogenic proteins expressed on the cell membrane at the threshold level needed for recognition. He also believed that immunogenic proteins that characterize a malignancy exist, but are only present at a fraction of the level needed to induce tumor destruction. By pooling tumor membrane proteins, we were able to define 3 specific oncofetal proteins expressed only during fetal life. Later in life a viral or carcinogenic agent reactivates the needed gene to produce a post translational modification of the oncofetal protein. The more common of these tumor immunogens to be identified was a modified form of MUC5ac, Monoclonals to this target were produced GMP, tested in vitro and based on the strong ADCC noted in contrast to a CD8 response, were introduced for use in clinical trials in patients with metastatic colorectal cancer having failed all standard forms of therapy.

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Cite the Article:

Arlen M, Arlen P, Dubeykovskiy A, Saric O, Coppa G, Conte C, et al. The Nature of Mutated Muc5ac, an Oncofetal Protein, Expressed in Colorectal Cancer: It’s Role as a Therapeutic Immunogen. Clin Oncol. 2016; 1: 1096.