2. Academic Validation
  3. Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses

Novel bispecific antibody-drug conjugate targeting PD-L1 and B7-H3 enhances antitumor efficacy and promotes immune-mediated antitumor responses

  • J Immunother Cancer. 2024 Oct 2;12(10):e009710. doi: 10.1136/jitc-2024-009710.
Yijun Dong # 1,  Zongliang Zhang # 2,  Siyuan Luan 3,  Meijun Zheng 1,  Zeng Wang 2,  Yongdong Chen 2,  Xiaoting Chen 4,  Aiping Tong 5,  Hui Yang 6
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head & Neck Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 3 Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
  • 4 Animal Experimental Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
  • 5 State Key Laboratory of Biotherapy and Cancer Center, Research Unit of Gene and Immunotherapy, Chinese Academy of Medical Sciences, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, China yh8806@163.com aipingtong@scu.edu.cn.
  • 6 Department of Otolaryngology-Head & Neck Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, China yh8806@163.com aipingtong@scu.edu.cn.
  • # Contributed equally.
PMID: 39357981 DOI: 10.1136/jitc-2024-009710
Abstract

Background: Antibody-drug conjugates (ADCs) offer a promising approach, combining monoclonal Antibodies with chemotherapeutic drugs to target Cancer cells effectively while minimizing toxicity.

Methods: This study examined the therapeutic efficacy and potential mechanisms of a bispecific ADC (BsADC) in laryngeal squamous cell carcinoma. This BsADC selectively targets the immune checkpoints programmed cell death ligand-1 (PD-L1) and B7-H3, and the precise delivery of the small-molecule toxin monomethyl Auristatin E.

Results: Our findings demonstrated that the BsADC outperformed its bispecific antibody and PD-L1 or B7-H3 ADC counterparts, particularly in terms of in vitro/in vivo tumor cytotoxicity, demonstrating remarkable immune cytotoxicity. Additionally, we observed potent activation of tumor-specific immunity and significant induction of markers of immunogenic cell death (ICD) and potential endoplasmic reticulum stress.

Conclusion: In conclusion, this novel BsADC, through Immune Checkpoint inhibition and promotion of ICD, amplified durable tumor immune cytotoxicity, providing novel insights and potential avenues for future Cancer treatments and overcoming resistance.

Keywords

Antibody-drug conjugates - ADC; Head and Neck Cancer; Immune Checkpoint Inhibitor.

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