Novel cancer-specific epidermal growth factor receptor antibody obtained from the serum of esophageal cancer patients with long-term survival

Although esophageal cancer has a poor prognosis after recurrence, some patients have shown long-term survival despite recurrence. We hypothesized that induction of either antitumor Abs or antitumor-specific CTLs could play a role in long-term survival (5 years or longer) in patients with recurrence and/or distant metastases. Therefore, we aimed to obtain Abs that specifically bind to cancer cells by using serum samples from patients with a good prognosis. A phage library was prepared using PBMC mRNA of the patients, and cell panning was carried out using an esophageal cancer cell line. Results showed the presence of an epidermal growth factor receptor (EGFR) Ab, KT112, that specifically bound to the cancer cell line. Notably, KT112 bound to only EGFR-positive cancer cells but failed to bind to normal esophageal cells. Furthermore, KT112 was characterized by responses to EGFR expressed on cancer cells but not to the recombinant extracellular domain of EGFR. Immunohistochemical analysis showed that KT112 reacted with 17.4% of esophageal squamous cell carcinoma tissue but not with any other cancer or normal tissue, suggesting that the Ab recognizes cancer-specific forms of EGFR and might have contributed to tumor suppression in patients with esophageal cancer. Furthermore, because of its high cancer specificity, KT112 could be a promising therapeutic option (e.g., in Ab-drug conjugates) for esophageal cancer.