Human Monoclonal Antibodies against Cytokeratin 18 Generated from Patients with Gastric Cancer

Abstract

By co‐culturing regional lymph node B‐cells and HAT‐sensitive mutant cells obtained from RPMI‐1788 cells, no less than 20,000 Epstein‐Barr (EB)‐transformed colonies were obtained from 32 patients with gastric cancer. From B‐cell cultures generating antibodies reactive with gastric cancer tissues as well as cultured gastric cancer cells, two EB‐transformed cell clones termed C418–59 and C1218–39 were isolated. Both of them produced human IgM‐class antibodies, termed Mab418–59 and Mab 1218–39, respectively. Both antibodies reacted with an antigen with a molecular weight of 45 kd existing in gastric cancer MKN‐45, MKN‐1, and Kato‐III cells, and also with all of 4 adenocarcinomas of the stomach in paraffin sections. The antigen recognized by both antibodies was identified as a kind of cytoskeletal protein, cytokeratin 18, In this study, it was confirmed that B‐cell clones generating autoantibodies against cytokeratin 18 were present in some patients with gastric cancer.

A Distinct Repertoire of Autoantibodies in Hepatocellular Carcinoma Identified by Proteomic Analysis

“…Circulating anti-cytokeratin 8 antibody immune complexes were reported in sera of patients with pulmonary fibrosis (30). The presence of autoantibodies directed against cytokeratin 18 has been observed in sera from patients with gastric cancer (31). Interestingly, transgenic mice that express a mutant form of cytokeratin 18 develop chronic hepatitis with a disruption of hepatocyte keratin filaments (32).…”

Serum M30 levels are associated with survival in advanced gastric carcinoma patients

“…Although there has been an important decline in mortality rates in recent years, there remains a high recurrence rate following primary therapy. Previously, it was reported that CK-18 expression was detected in tissue blocks of some patients with gastric carcinoma [13] . Recently, Xu et al [14] showed that gastric carcinoma patients had over-expression of CK-18 mRNA while patients with benign gastric pathologies such as gastric ulcers did not.…”

Mapping and regulation of the tumor-associated epitope recognized by mAb RS-11

“…RS-11 was developed by immunization of rats with a syngeneic bladder tumor and its isotype is IgM. Interestingly, there are several reports that mAbs generated using autologous lymphocytes of tumor-bearing patients recognize keratin 8 or keratin 18 (35)(36)(37)(38). The isotypes of these mAbs are all IgM.…”