PD-L1-Binding Antigen Presenters: Redirecting Vaccine-Induced Antibodies for Tumor-Agnostic Immunotherapy
摘要
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-gE) has been engineered to tether varicella-zoster virus 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 Trastuzumab and Kadcyla to kill Human Epidermal growth factor Receptor 2 (HER2)-negative, PD-L1-positive cells. This strategy represents an innovative strategy for enhancing PD-L1-targeted therapies by leveraging pre-existing antibodies induced by viral infections or vaccines, alongside commercially available antibody-based therapies.
参考文献
[1] O'reilly M A. Exploiting the mechanical effects of ultrasound for noninvasive therapy[J]. Science, 2024,385(6714):eadp7206.
[2] Sboros V. Response of contrast agents to ultrasound[J]. Advanced drug delivery reviews, 2008, 60(10):1117-1136.
[3] Faez T, Emmer M, Kooiman K, et al. 20 years of ultrasound contrast agent modeling[J]. IEEE transactions on ultrasonics, ferroelectrics, and frequency control, 2012,60(1):7-20.
[4] Coussios C C, Roy R A. Applications of acoustics and cavitation to noninvasive therapy and drug delivery[J]. Annu Rev Fluid Mech, 2008, 40(1): 395-420.
[5] Cattaneo M, Guerriero G, Shakya G,et al. Cyclic jetting enables microbubble-mediated drug delivery[J].Nature Physics,2025,21(4):590-598.
[6] Chen H, Kreider W, Brayman A A, et al. Blood vessel deformations on microsecond time scales by ultrasonic cavitation[J]. Physical review letters, 2011, 106(3): 034301.
[7] Fan Y, Ohl C-D. Perforation of thin-membrane-covered soft matter induced by cavitation-initiated extreme mechanics[J]. Physical Review Applied, 2025, 23(2): 024052.
[8] Ohl C-D, Arora M, Ikink R, et al. Sonoporation from jetting cavitation bubbles[J]. Biophysical journal,2006,91(11):4285-4295.
[9] Li F, Yang C, Yuan F,et al. Dynamics and mechanisms of intracellular calcium waves elicited by tandem bubble-induced jetting flow[J]. Proc Natl Acad Sci U S A, 2018, 115(3): E353-e362.
[10] Maeda K, Colonius T. Bubble cloud dynamics in an ultrasound field[J]. Journal of fluid mechanics, 2019,862:1105-1134.
指标
DOI：
Submission ID：
下载次数
已发布
如何引用
下载引用
利益冲突声明
作者声明无任何需要披露的利益冲突。
Copyright
本预印本的版权持有者为作者/资助方。
保留所有权利。本作品受版权保护。未经版权所有者事先书面许可，不得以任何形式或方式复制、分发或传播本作品的任何部分。