journal article·2024-08Open access

Epigenetic Reprogramming Potentiates ICAM1 Antibody Drug Conjugates in Preclinical Models of Melanoma

Peng Zhang, Changjuan Tao, Ye Lu, Peijing Li, Xing Wang, Yujie Dai, Yun Xi, Takaya Shimura, Xinfang Li, Jianmin Fang, Liu Yang, Dawei He, Peng Guo

Advanced Science· Volume 11· Issue 30

Abstract

Abstract Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1‐DXd) is elucidated. DAC treatment significantly enhanced anti‐tumor efficacy of I1‐DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1‐DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.
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Research context

OpenAlex topics: CAR-T cell therapy research · Protein Degradation and Inhibitors · Cancer Immunotherapy and Biomarkers

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Medical Oncology Zhejiang Provincial People's Hospital Hangzhou Zhejiang 310022 China

Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province Zhejiang Provincial People's Hospital People's Hospital of Hangzhou Medical College Hangzhou Zhejiang 310014 China

Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences Hangzhou Zhejiang 310022 China

Department of Radiation Oncology The Cancer Hospital of the University of Chinese Academy of Sciences Zhejiang Cancer Hospital Hangzhou Zhejiang 310022 China

Key Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province Zhejiang Cancer Hospital Hangzhou Zhejiang 310022 China

Department of Head and Neck Surgery The Cancer Hospital of the University of Chinese Academy of Sciences Zhejiang Cancer Hospital Hangzhou Zhejiang 310022 China

MabPlex International Yantai Shandong 264006 China

Department of Pathology The Cancer Hospital of the University of Chinese Academy of Sciences Zhejiang Cancer Hospital Hangzhou Zhejiang 310022 China

Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya 467–8601 Japan

School of Materials Science and Engineering Tianjin University Tianjin 300072 China

Department of Urology Children's Hospital of Chongqing Medical University Chongqing China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Medical Science and Technology Project of Zhejiang Province · Science Fund for Distinguished Young Scholars of Zhejiang Province · Natural Science Foundation of Zhejiang Province

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