Crystal structure of the Fab fragment of gemtuzumab ozogamicin, the first approved antibody-drug conjugate for induction therapy of AML

• 영문명: Crystal structure of the Fab fragment of gemtuzumab ozogamicin, the first approved antibody-drug conjugate for induction therapy of AML
• 발행기관: 한국구조생물학회
• 저자명: Seung Beom Choi Yu-Jeong Jang Nahyeon Gu Yong-Seok Heo
• 간행물 정보: 『Biodesign』Vol 11, No 4, Dec, 55~58쪽, 전체 4쪽
• 주제분류: 자연과학 > 생물학
• 파일형태: PDF
• 발행일자: 2023.12.31

영문 초록

Gemtuzumab ozogamicin is an antibody-drug conjugate consisting of a toxin chemically bound to an antibody that detects the CD33 protein on tumor cells. CD33 is a myeloid differentiation antigen displayed on acute myeloid leukemia (AML) blasts in most patients and has thus been highlighted as a potential target. When administrated to AML patients, gemtuzumab binds to CD33 and facilitates the uptake of the toxic payload into the cells, leading to cell death. Here, the crystal structure of the gemtuzumab Fab was determined to 2.50 Å resolution, with R/Rfree = 0.191/0.219. The five complementarity determining regions (CDRs) of gemtuzumab but the CDR1 of the heavy chain (HCDR1) are clearly displayed in the structure with apparent electron density. The results of this structural study may aid in predicting the binding mode of gemtuzumab to CD33, supporting the development of an ADC with increased therapeutic potency for the treatment of AML.

목차

INTRODUCTION

RESULTS AND DISCUSSION

METHODS

ACKNOWLEDGEMENTS

CONFLICT OF INTEREST

AUTHOR INFORMATION

REFERENCES