Abstract 2297: Anti-labyrinthin monoclonal antibody reduces human adenocarcinoma circulating tumor cells in the blood of patient-derived xenograft models and inhibits the growth of adenocarcinoma cell cultures

Abstract

Abstract Labyrinthin is a 255-amino acid protein antigen that is expressed on the cell-surface of most adenocarcinoma tumors and is not expressed on the surface of most normal cells, which makes it an attractive candidate for targeted therapy. Originally, labyrinthin had been deduced to be a product of a large deletion in the gene coding for junctate. We found that the junctate gene in labyrinthin-expressing adenocarcinoma cells does not have any deletion, and we propose that the labyrinthin protein is a splice variant of the junctate gene. This study aimed to determine the effects of an anti-labyrinthin monoclonal antibody, on adenocarcinoma cells in vitro and on patient-derived xenograft (PDX) models in vivo. Lung, breast and colorectal adenocarcinoma cell lines, as well as a primary-cell culture of a colorectal adenocarcinoma patient, were assessed for cell surface expression of labyrinthin. The cells were then incubated in the presence of the anti-labyrinthin antibody and growth rate was monitored by live imaging methods. Untreated primary-cell cultures of the colorectal adenocarcinoma patient were also grafted to immunodeficient mice to produce PDX tumors. When establishment of palpable tumors was observed, the mice were injected with the antibody. Peripheral blood was sampled from the mice and circulating tumor cells (CTCs) were quantified by flow cytometry. A significant reduction of approximately 60% was detected in the number of CTCs in the peripheral blood of the antibody-treated PDX mice compared to untreated control PDX mice. Additionally, a significant reduction was measured in the growth-rate of cultured primary cells and in lung, breast and colorectal adenocarcinoma cell lines in the presence of the antibody. We conclude that the anti-labyrinthin antibody has an inhibitory effect on the formation of adenocarcinoma CTCs in vivo as well as on the growth rate of cultured adenocarcinoma tumor cells. Citation Format: Natalia Saleev, Netta R. Blondheim-Shraga, Evgeny Solomonov, Shiran Shapira, Izhak Haviv, Solomon M. Stemmer, Hanoch Slor. Anti-labyrinthin monoclonal antibody reduces human adenocarcinoma circulating tumor cells in the blood of patient-derived xenograft models and inhibits the growth of adenocarcinoma cell cultures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2297.