A novel high-affinity human monoclonal antibody to mesothelin.

International Journal of Cancer. Journal International Du Cancer
Mitchell HoIra Pastan

Abstract

Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of mesothelioma, ovarian cancer and other malignant tumors. The interaction between mesothelin and CA125 (also called MUC16) may facilitate the implantation and metastasis of tumors in the peritoneal cavity. A desirable therapeutic agent involves finding a fully human monoclonal antibody (mAb) that binds to mesothelin or CA125 and inhibits their interaction. Here, we report the identification of a novel human mAb to mesothelin. HN1, a human single-chain Fv specific for mesothelin, was isolated from a naïve human single-chain variable fragment (scFv) phage display library. To investigate HN1 as a potential therapeutic, we generated a fully human IgG with the γ 1 heavy chain and the κ light chain and an immuntoxin by fusing the HN1 scFv to a truncated Pseudomonas exotoxin A. The HN1 IgG kills cancer cells with very strong antibody-dependent cell-mediated cytotoxicity. HN1 binds a conformation-sensitive epitope in human mesothelin with high affinity (K(D) = 3 nM). The HN1 epitope is different from that of SS1, a mouse Fv used to develop therapeutic antibodies that are currently in clinical trials. HN1 binds to cell surfa...Continue Reading

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Citations

Sep 29, 2011·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Mitchell Ho
Apr 6, 2011·Immunotherapy·Lindzy F DodsonPeter Goedegebuure
May 26, 2011·Journal of Cancer·Xinran XiangMitchell Ho
Feb 5, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Wei GaoMitchell Ho
Aug 8, 2015·Journal of Cancer Research and Clinical Oncology·Haojun ShiDeliang Fu
Dec 9, 2014·Human Vaccines & Immunotherapeutics·Amedeo AmedeiDomenico Prisco
Jan 30, 2013·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Jenette CreaneyBruce W S Robinson
Mar 20, 2013·BioMed Research International·Elena NiccolaiAmedeo Amedei
Oct 22, 2014·International Journal of Colorectal Disease·Shoubo CaoYan Yu
Dec 24, 2017·Scientific Reports·Gwendlyn KollmorgenGerhard Niederfellner
May 17, 2014·Expert Review of Anticancer Therapy·Sabina Antonela AntoniuDidona Ungureanu
Aug 30, 2019·Biomarker Research·Jiang Lv, Peng Li
Oct 28, 2015·Cancer Discovery·Aurore MorelloPrasad S Adusumilli
Jun 13, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Edmund K MoonSteven M Albelda

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