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

Abstract

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.

Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy

“…We did not generate many GBM-specific antibodies. Other strategies such as phage-display technology 48 could be applied to identify GBM-specific mAbs, although phage-display using whole cell panning is complicated by low target antigen density, high background due to irrelevant antigens, and nonspecific binding of phage particles to cell surfaces. 49 We obtained antibodies of mouse origin that might not be optimal for the generation of CAR-T cells for infusion in humans.…”

Advancements in ovarian cancer immunodiagnostics and therapeutics via phage display technology

“…Utilizing immune phage display libraries from humans, researchers compile extensive antibody gene repertoires from cancer patients to isolate antibodies with specific binding capabilities ( 27 ). Studies include constructing scFv libraries from patient PBMCs, identifying high-affinity antibodies to EphA2 ( 28 ), and using cell panning to bind EGFR-affine fragments to esophageal cancer cells ( 29 ). Further developments involve producing nanobodies targeting HIF-1 and CD20/CD3 bispecific nanobodies from immunized camels, showing potential in cancer diagnostics and treatment ( 30 – 32 ).…”