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  3. PD-L1-Binding Antigen Presenters: Redirecting Vaccine-Induced Antibodies for Cancer Immunotherapy

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

  • Adv Sci (Weinh). 2026 Apr;13(20):e19574. doi: 10.1002/advs.202519574.
Huixin Gao 1,  Lijuan Lu 2,  Xiaoxiao Xiong 3,  Yi Li 3,  Donghui Hu 4,  Duo Zhang 3,  Zhiwei Feng 3,  Cong Liu 3,  Nannan Liu 3,  Xiaoli Li 3,  Jizhou Tan 5,  Ting Liu 6,  Ling Peng 7,  Lu Lu 7,  Huiyi Feng 8,  Yan Zhong 9,  Guisen Tan 10,  Zhicheng Zhang 11,  Liqin Huang 12,  Chao Su 13,  Ying Xue 3,  Shuo Song 14,  Wenxia Fan 3,  Wei Wang 15,  Fan Zou 3
Affiliations

Affiliations

  • 1 Department of Clinical Laboratory, Guangzhou Women and Children Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
  • 2 Department of Medical Oncology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, P. R. China.
  • 3 Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen, Guangdong, P.R. China.
  • 4 Department of Traditional Chinese Medicine, The Third People's Hospital of Hubei Province, Wuhan, Hubei, P.R. China.
  • 5 The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China.
  • 6 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.
  • 7 Beijing Luzhu Biotechnology Co. Ltd., Beijing, P.R. China.
  • 8 Department of Oncology, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, P.R. China.
  • 9 Department of Pathology, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, P.R. China.
  • 10 The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China.
  • 11 Zhongshan Institute for Drug Discovery, Zhongshan, Guangdong, P.R. China.
  • 12 Shenzhen Blood Center, Shenzhen, Guangdong, P.R. China.
  • 13 Jilin Province Jilin Hospital of Integrated Traditional Chinese and Western Medicine, Jilin, Jilin, P.R. China.
  • 14 Faculty of Life and Health Sciences, Shenzhen University of Advanced Technology, Shenzhen, Guangdong, P.R. China.
  • 15 Department of Thoracic Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, P.R. China.
PMID: 41668552 DOI: 10.1002/advs.202519574
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.

Keywords

PD‐L1 targeted immunotherapy; PD‐L1‐binding antigen presenter (PBAP); antibody drug conjugates (ADC); antibody‐dependent cellular cytotoxicity (ADCC); vaccine‐induced antibodies.

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