2. Academic Validation
  3. Reprogramming the Tumor Immune Microenvironment with ICAM-1-Targeted Antibody‒Drug Conjugates and B7-H3-CD3 Bispecific Antibodies

Reprogramming the Tumor Immune Microenvironment with ICAM-1-Targeted Antibody‒Drug Conjugates and B7-H3-CD3 Bispecific Antibodies

  • Adv Sci (Weinh). 2025 Feb 25:e2415577. doi: 10.1002/advs.202415577.
Shoubing Zhou 1 2,  Mengyu Hong 3,  Dan Zhao 3,  Wenyu Li 1 2,  Xiaolong Yuan 1 2,  Yinghong Wang 1 2,  Hualong Li 4,  Yang Yang 5 6,  Tengchuan Jin 3 7 8 9 10,  Jing Pan 1 2
Affiliations

Affiliations

  • 1 Department of Breast Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230031, China.
  • 2 Department of Breast Oncology, Anhui Provincial Cancer Hospital, Hefei, Anhui, 230031, China.
  • 3 Laboratory of Structural Immunology, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, China.
  • 4 Department of Tumor Radiotherapy, People Hospital of Fengyang County, Chuzhou, Anhui, 233100, China.
  • 5 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
  • 6 Department of Oncology, Suzhou Hospital of Anhui Medical University, Suzhou, 234000, China.
  • 7 Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, University of Science and Technology of China, Hefei, Anhui, 230001, China.
  • 8 Institute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, Anhui, China.
  • 9 Biomedical Sciences and Health Laboratory of Anhui Province, University of Science & Technology of China, Hefei, 230027, China.
  • 10 Clinical Research Hospital of the Chinese Academy of Sciences (Hefei), University of Science and Technology of China, Hefei, 230001, China.
PMID: 39996528 DOI: 10.1002/advs.202415577
Abstract

Reprogramming the tumor immune microenvironment (TIM) plays an important role in promoting the reversal of immune "cold" tumors into "hot" inflammatory tumors. Improving drug targeting, blocking immune checkpoints, and promoting the activation of immune cells are crucial for reprogramming the TIM. Here, an intercellular adhesion molecule 1-targeted antibody‒drug conjugate in combination with a B7-H3-CD3 bispecific antibody is selected for TIM reprogramming, which improved the efficacy of triple-negative breast Cancer Immunotherapy. This combination therapy improves drug targeting, blocks immune checkpoint pathways, and activates effector T cells to release cytokines, leading to immunogenic cell death and the release of tumor-associated antigens. This effect promotes the maturation of dendritic cells, infiltration and activation of cytotoxic CD8+ T cells, repolarization of M1-type macrophages, and reduction of M2-type macrophages, immune suppressor Tregs, and MDS cells, thereby reprogramming the TIM. In addition, this innovative strategy promotes the accumulation of immune cells at metastasis sites and significantly impedes the progression of lung metastatic lesions. Overall, this study provides novel insights for reprogramming the TIM using novel immunotherapeutic strategies that leverage the synergistic effects of antibody-drug conjugates and bispecific antibodies.

Keywords

B7‐H3‐CD3; ICAM‐1; antibody‒drug conjugates; triple‐negative breast cancer, tumor immune microenvironment.

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