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journal article·2026-04Open access

PD‐L1‐Binding Antigen Presenters: Redirecting Vaccine‐Induced Antibodies for Cancer Immunotherapy

Huixin Gao, Lijuan Lu, Xiaoxiao Xiong, Yi Li, Donghui Hu, Duo Zhang, Zhiwei Feng, Cong Liu, Nannan Liu, Xiaoli Li, Jizhou Tan, Ting Liu, Ling Peng, Lu Lu, Huiyi Feng, Yan Zhong, Guisen Tan, Zhicheng Zhang, Liqin Huang, Chao Su, Ying Xue, Shuo Song, Wenxia Fan, Wei Wang, Fan Zou

Advanced Science· Volume 13· Issue 20
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Source abstract

Abstract

ABSTRACT The efficacy of immunotherapy in enhancing antitumor immunity in solid tumors remains limited, primarily due to the insufficient immunogenicity of tumor cells. In contrast, vaccination and natural viral infections can generate durable, high‐titer antiviral antibodies. A modular Programmed Death‐Ligand 1 (PD‐L1)‐binding antigen presenter (PBAP) has been engineered to tether varicella‐zoster virus (VZV) glycoprotein E (gE) to PD‐L1 expressed on tumor cell surfaces. This innovative construct leverages pre‐existing anti‐gE antibodies to trigger antibody‐dependent effector mechanisms. PBAP‐gE effectively bound to PD‐L1 positive tumor cells and, together with vaccine‐induced anti‐gE antibodies, potentiated NK cell‐mediated antibody‐dependent cellular cytotoxicity (ADCC) in vitro and induced significant tumor regression in murine models. The PBAP platform is modular and versatile. For example, a PBAP‐HER2 construct synergized with Herceptin and Kadcyla to eliminate human epidermal growth factor receptor 2 (HER2)‐negative, PD‐L1 positive cells. This work represents an innovative strategy for enhancing PD‐L1‐targeted therapies by leveraging pre‐existing antibodies induced by vaccination or natural viral infections, alongside commercially available antibody‐based therapies. Given the broad expression of PD‐L1 across various solid tumors and hematologic malignancies, our strategy holds promise as a potentially widely applicable platform for diverse PD‐L1‐positive patient populations.
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Research context

OpenAlex topics: Cancer Immunotherapy and Biomarkers · CAR-T cell therapy research · Monoclonal and Polyclonal Antibodies Research

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

Affiliations

Department of Clinical Laboratory Guangzhou Women and Children Medical Center Guangzhou Medical University Guangzhou Guangdong P.R. China

Department of Medical Oncology the Third Affiliated Hospital of Sun Yat‐Sen University Guangzhou Guangdong P. R. China

Faculty of Pharmaceutical Sciences Shenzhen University of Advanced Technology Shenzhen Guangdong P.R. China

Department of Traditional Chinese Medicine The Third People's Hospital of Hubei Province Wuhan Hubei P.R. China

The First Affiliated Hospital Sun Yat‐sen University Guangzhou P.R. China

The Second Clinical Medical College Clinical Laboratory/State Key Laboratory of Traditional Chinese Medicine Syndrome Guangzhou University of Chinese Medicine Guangdong Provincial Hospital of Chinese Medicine Guangzhou P.R. China

Beijing Luzhu Biotechnology Co. Ltd. Beijing P.R. China

Department of Oncology Shenzhen Hospital of Southern Medical University Shenzhen Guangdong P.R. China

Department of Pathology Shenzhen Hospital of Southern Medical University Shenzhen Guangdong P.R. China

The First Affiliated Hospital of Guilin Medical University Guilin Guangxi P.R. China

Zhongshan Institute for Drug Discovery Zhongshan Guangdong P.R. China

Shenzhen Blood Center Shenzhen Guangdong P.R. China

Jilin Province Jilin Hospital of Integrated Traditional Chinese and Western Medicine Jilin Jilin P.R. China

Faculty of Life and Health Sciences Shenzhen University of Advanced Technology Shenzhen Guangdong P.R. China

Department of Thoracic Surgery the Second Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong P.R. China

Funding

Shenzhen Science and Technology Innovation Program · National Natural Science Foundation of China · Natural Science Foundation of Guangdong Province · Sanming Project of Medicine in Shenzen Municipality

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