The terminal sialic acid of stage-specific embryonic antigen-4 has a crucial role in binding to a cancer-targeting antibody

Caroline Soliman,Jia Xin Chua,Mireille Vankemmelbeke,Richard S Mcintosh,Andrew J Guy,Ian Spendlove,Lindy G Durrant,Paul A Ramsland

doi:10.1016/s0021-9258(17)49911-x

Abstract

The terminal sialic acid of stage-specific embryonic antigen-4 has a crucial role in binding to a cancer-targeting antibody

Highlights

It has long been known that glycosylation of malignant cells differs significantly to that of healthy cells [1]
Overexpression of ST3GAL2 has been implicated in poor outcomes for various cancers, including breast and ovarian cancer, which suggests a potential role of SSEA4 in the development or maintenance of a tumor environment [16,18]
Our findings from crystallography and molecular dynamics simulations explain the basis for ch28/11 monoclonal antibodies (mAbs) specificity for Stage-specific embryonic antigen-4 (SSEA-4) and identify a critical role for the terminal sialic acid, which is not present in SSEA-3, in antibody recognition

Summary

INTRODUCTION

It has long been known that glycosylation of malignant cells differs significantly to that of healthy cells [1]. GSLs are often overexpressed in various types of human malignancies, including GD2 and GD3 in melanoma [9,10] and Globo-H in breast and ovarian cancers [11]. Stage-specific embryonic antigens (SSEAs) are a family of glycoconjugate antigens, consisting of SSEA-1 ( known as CD15 or Lewis X), and two related GSLs SSEA-3 ( known as Gb5Cer) and SSEA-4 ( known as sialylGb5Cer) [12] Both SSEA-3 and SSEA-4 are known cell surface markers of human embryonic and pluripotent stem cells. Overexpression of ST3GAL2 has been implicated in poor outcomes for various cancers, including breast and ovarian cancer, which suggests a potential role of SSEA4 in the development or maintenance of a tumor environment [16,18]. Our findings from crystallography and molecular dynamics simulations explain the basis for ch28/11 mAb specificity for SSEA-4 and identify a critical role for the terminal sialic acid, which is not present in SSEA-3, in antibody recognition

RESULTS

DISCUSSION

FIGURES AND FIGURE LEGENDS