Eliminating VEGFA+ Tumor-associated Neutrophils by Antibody-drug Conjugates Boosts Antitumor Immunity and Potentiates PD-1 Immunotherapy in Preclinical Models of Cervical Cancer

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2025 Feb 19

PMID 39971940

Authors

Shili Yao

Lu Sun

Ye Lu

Xiu Zhu

Rui Xu

Tong Yang

Huarong Tang

Peng Guo

Tao Zhu

Affiliations

Soon will be listed here.

Abstract

Tumor-associated neutrophils (TANs) actively interact with antibody-drug conjugates (ADCs) within the tumor microenvironment (TME), though the detailed mechanisms governing their response to ADC treatment remain to be fully elucidated. Herein, we explored how ICAM1-targeted ADCs affect TAN dynamics in preclinical models of cervical cancer. We discovered that I-DXd, our in-house ADC targeting cervical cancer, effectively eliminates tumor cells through specific antigen recognition while concurrently depleting pro-tumor VEGFA + TANs via Fcγ receptor-mediated phagocytosis. This dual action promotes an immunologically favorable TME. Through comprehensive preclinical studies, we established a foundational understanding of the synergistic benefits of combining I-DXd treatment with PD-1 immune checkpoint inhibition, thereby opening new avenues for therapeutic intervention in advanced cervical cancer.

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