한빛사논문
- 조회598
Jiyoon Bu a,b,1, Woo-jin Jeong a,b,1, Roya Jafari c, Luke J. Kubiatowicz a, Ashita Nair a, Michael J. Poellmann a, Rachel S. Hong a, Elizabeth W. Liu a, Randall H. Owen a, Piper A. Rawding a, Caroline M. Hopkins a, DaWon Kim a, Daniel J. George d,e, Andrew J. Armstrong d,e, Petr Kralc,l, Andrew Z. Wang f,m, Justine Bruce g,h, Tian Zhang d,e,k, Randall J. Kimple g,h, Seungpyo Hong a,h,i,j,*
a Pharmaceutical Sciences Division and Wisconsin Center for NanoBioSystems (WisCNano), School of Pharmacy, University of Wisconsin – Madison, 777 Highland Ave, Madison, WI, 53705, USA b Department of Biological Sciences and Bioengineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 22212, Republic of Korea c Department of Chemistry, University of Illinois at Chicago, 845 W Taylor St, Chicago, IL, 60607, USA d Department of Medicine, Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, 10 Bryan Searle Drive, Durham, NC, 27710, USA e Duke Cancer Institute Center for Prostate and Urologic Cancers, Duke University, 20 Duke Medicine Cir, Durham, NC, 27710, USA f Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA g Department of Human Oncology, University of Wisconsin-Madison, Madison, 600 Highland Ave, WI, 53792, USA h UW Carbone Cancer Center, University of Wisconsin-Madison, Madison, 600 Highland Ave, WI, 53792, USA i Department of Biomedical Engineering, The University of Wisconsin-Madison, 1550 Engineering Dr., Madison, WI, 53705, USA j Yonsei Frontier Lab, Department of Pharmacy, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea k Department of Internal Medicine and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA l Department of Physics, Department of Pharmaceutical Sciences, University of Illinois at Chicago, 845 W Taylar St, Chicage, IL, 60607, USA m Department of Radiation Oncology and Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA
* Corresponding author.
1 Jiyoon Bu and Woo-jin Jeong contributed equally to this work.
Abstract
Despite its high potential, PD-L1 expressed by tumors has not been successfully utilized as a biomarker for estimating treatment responses to immunotherapy. Circulating tumor cells (CTCs) and tumor-derived exosomes that express PD-L1 can potentially be used as biomarkers; however, currently available assays lack clinically significant sensitivity and specificity. Here, a novel peptide-based capture surface is developed to effectively isolate PD-L1-expressing CTCs and exosomes from human blood. For the effective targeting of PD-L1, this study integrates peptide engineering strategies to enhance the binding strength and specificity of a β-hairpin peptide derived from PD-1 (pPD-1). Specifically, this study examines the effect of poly(ethylene glycol) spacers, the secondary peptide structure, and modification of peptide sequences (e.g., removal of biologically redundant amino acid residues) on capture efficiency. The optimized pPD-1 configuration captures PD-L1-expressing tumor cells and tumor-derived exosomes with 1.5-fold (p = 0.016) and 1.2-fold (p = 0.037) higher efficiencies, respectively, than their whole antibody counterpart (aPD-L1). This enhanced efficiency is translated into more clinically significant detection of CTCs (1.9-fold increase; p = 0.035) and exosomes (1.5-fold increase; p = 0.047) from patients' baseline samples, demonstrating stronger correlation with patients’ treatment responses. Additionally, we confirmed that the clinical accuracy of our system can be further improved by co-analyzing the two biomarkers (bimodal CTC/exosome analysis). These data demonstrate that pPD-1-based capture is a promising approach for capturing PD-L1-expressing CTCs and exosomes, which can be used as a reliable biomarker for cancer immunotherapy.
논문정보
- Research article
- 2022년 10월 (BRIC 등록일 2022-09-27)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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