Cancer Research and Treatment

Original Articles

General

Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy: Yilei Chen, Hongxing Huang, Yin Liu, Zhanghao Wang, Lili Wang, Quanxiao Wang, Yan Zhang, Hua Wang; Cancer Res Treat. 2022;54(2):362-374. Published online August 3, 2021; DOI: https://doi.org/10.4143/crt.2021.424

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Purpose
The purpose of this study was to optimize a peptide (nABP284) that binds to programmed cell death protein 1 (PD-1) by a computer-based protocol in order to increase its affinity. Then, this study aimed to determine the inhibitory effects of this peptide on cancer immune escape by coculturing improving cytokine-induced killer (ICIK) cells with cancer cells.
Materials and Methods
nABP284 that binds to PD-1 was identified by phage display technology in our previous study. AutoDock and PyMOL were used to optimize the sequence of nABP284 to design a new peptide (nABPD1). Immunofluorescence was used to demonstrate that the peptides bound to PD-1. Surface plasmon resonance was used to measure the binding affinity of the peptides. The blocking effect of the peptides on PD-1 was evaluated by a neutralization experiment with human recombinant programmed death-ligand 1 (PD-L1) protein. The inhibition of activated lymphocytes by cancer cells was simulated by coculturing of human acute T lymphocytic leukemia cells (Jurkat T cells) with human tongue squamous cell carcinoma cells (Cal27 cells). The anticancer activities were determined by coculturing ICIK cells with Cal27 cells in vitro.
Results
A high-affinity peptide (nABPD1, K_D=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (K_D=11.8 μM). nABPD1 showed better efficacy than nABP284 in terms of increasing the secretion of interkeulin-2 by Jurkat T cells and enhancing the in vitro antitumor activity of ICIK cells.
Conclusion
nABPD1 possesses higher affinity for PD-1 than nABP284, which significantly enhances its ability to block the PD-1/PD-L1 interaction and to increase ICIK cell-mediated antitumor activity by armoring ICIK cells.

Citations

Citations to this article as recorded by

Peptide‑based therapeutic strategies for glioma: Current state and prospects
Yajing Mi, Pengtao Jiang, Jing Luan, Lin Feng, Dian Zhang, Xingchun Gao
Peptides.2025; 185: 171354. CrossRef
Development of Novel Short Peptide Inhibitor Targeted to Immune Checkpoint PD-1 LBD
Xingyan Zhu, Yuping Wei, Man Zhang, Kun Liu, Ziyang Liu, Qiuhong Niu
International Journal of Peptide Research and Therapeutics.2025;[Epub] CrossRef
Cholesterol-modified peptide nanomicelles as a promising platform for cancer therapy: A review
Kodzo Prosper Adzavon, Weijian Zhao, Sameena Noor Khattak, Wang Sheng
International Journal of Biological Macromolecules.2025; 311: 143456. CrossRef
A novel bispecific peptide targeting PD-1 and PD-L1 with combined antitumor activity of T-cells derived from the patients with TSCC
Lili Wang, Junheng Zheng, Zhihao Tan, Yan Zhang, Hua Wang
International Immunopharmacology.2024; 138: 112582. CrossRef
Peptide Blockers of PD-1-PD-L1 Interaction Reinvigorate PD-1-Suppressed T Cells and Curb Tumor Growth in Mice
Shanshan (Jenny) Zhong, Xiaoling Liu, Tomonori Kaneko, Yan Feng, Owen Hovey, Kyle Yang, Sally Ezra, Soon-Duck Ha, Sung Kim, John K. McCormick, Huadong Liu, Shawn Shun-Cheng Li
Cells.2024; 13(14): 1193. CrossRef
Melittin-incorporated nanomedicines for enhanced cancer immunotherapy
Xuefeng Duan, Haoyang Zou, Jiazhen Yang, Shixian Liu, Tianmin Xu, Jianxun Ding
Journal of Controlled Release.2024; 375: 285. CrossRef
Peptides as multifunctional players in cancer therapy
Sri Murugan Poongkavithai Vadevoo, Smriti Gurung, Hyun-Su Lee, Gowri Rangaswamy Gunassekaran, Seok-Min Lee, Jae-Won Yoon, Yun-Ki Lee, Byungheon Lee
Experimental & Molecular Medicine.2023; 55(6): 1099. CrossRef
Progress of research on PD-1/PD-L1 in leukemia
Huizhen Cao, Tianyu Wu, Xue Zhou, Shuyang Xie, Hongfang Sun, Yunxiao Sun, Youjie Li
Frontiers in Immunology.2023;[Epub] CrossRef
Development of PD-1 blockade peptide-cell conjugates to enhance cellular therapies for T-cell acute lymphoblastic leukemia
Quanxiao Wang, Hongxing Huang, Peisheng Liang, Lili Wang, Junheng Zheng, Yan Zhang, Hua Wang
Medical Oncology.2023;[Epub] CrossRef
Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade
Won Suk Lee, Dong Sung Kim, Jeong Hun Kim, Yoonki Heo, Hannah Yang, Eun-Jin Go, Jin Hyoung Kim, Seung Joon Lee, Byung Cheol Ahn, Jung Sun Yum, Hong Jae Chon, Chan Kim
Journal for ImmunoTherapy of Cancer.2022; 10(6): e004799. CrossRef

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Hematologic Malignancy

Baseline Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured on ¹⁸F-FDG PET-CT Predict Outcomes in T-Cell Lymphoblastic Lymphoma: Xiaoyan Feng, Xin Wen, Ling Li, Zhenchang Sun, Xin Li, Lei Zhang, Jingjing Wu, Xiaorui Fu, Xinhua Wang, Hui Yu, Xinran Ma, Xudong Zhang, Xinli Xie, Xingmin Han, Mingzhi Zhang; Cancer Res Treat. 2021;53(3):837-846. Published online December 2, 2020; DOI: https://doi.org/10.4143/crt.2020.123

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Purpose
There is no optimal prognostic model for T-cell lymphoblastic lymphoma (T-LBL). Here, we discussed the predictive value of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on 18F-fluorodeoxyglucose positron emission tomography–computed tomography (PET-CT) in T-LBL.
Materials and Methods
Thirty-seven treatment naïve T-LBL patients with PET-CT scans were enrolled. TMTV was obtained using the 41% maximum standardized uptake value (SUVmax) threshold method, and TLG was measured as metabolic tumor volume multiplied by the mean SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by the log-rank test.
Results
The optimal cutoff values for SUVmax, TMTV, and TLG were 12.7, 302 cm3, and 890, respectively. A high SUVmax, TMTV, and TLG indicated a shorten PFS and OS. On multivariable analysis, TMTV ≥ 302 cm3, and central nervous system (CNS) involvement predicted inferior PFS, while high SUVmax, TLG and CNS involvement were associated with worse OS. Subsequently, we generated a risk model comprising high SUVmax, TMTV or TLG and CNS involvement, which stratified the population into three risk groups, which had significantly different median PFS of not reached, 14 months, and 7 months for low-risk group, mediate-risk group, and high-risk group, respectively (p < 0.001). Median OS were not reached, 27 months, and 13 months, respectively (p < 0.001).
Conclusion
Baseline SUVmax, TMTV, and TLG measured on PET-CT are strong predictors of worse outcome in T-LBL. A risk model integrating these three parameters with CNS involvement identifies patients at high risk of disease progression.

Citations

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A novel prognostic model utilizing TMTV and SUVmax from 18F-FDG PET/CT for predicting overall survival in patients with extranodal NK/T- cell lymphoma
Hua Wang, Demei Feng, Yiwen Mo, Huangming Hong, Yingying Hu, Li Huang, Xiaolei Wei, Yajun Li, Haibin Huang, Runhui Zheng, Yonghua Li, Hui Zeng, Robert Peter Gale, Tian Ying, Jing Guo, Zhenshu Xu, Wei Fan, Tongyu Lin
BMC Cancer.2025;[Epub] CrossRef
Metabolic parameters predict survival and toxicity in chimeric antigen receptor T‐cell therapy‐treated relapsed/refractory large B‐cell lymphoma
Hazim S. Ababneh, Andrea K. Ng, Jeremy S. Abramson, Jacob D. Soumerai, Ronald W. Takvorian, Matthew J. Frigault, Chirayu G. Patel
Hematological Oncology.2024;[Epub] CrossRef
Diagnosis of bone marrow involvement in angioimmunoblastic T-cell lymphoma should be based on both [ 18 F]FDG-PET/CT and bone marrow biopsy findings
Xinyu Liang, Chunli Yang, Minggang Su, Liqun Zou
Current Medical Research and Opinion.2024; 40(5): 803. CrossRef
The Role of Pre-therapeutic 18F-FDG PET/CT in Pediatric Hemophagocytic Lymphohistiocytosis With Epstein-Barr Virus Infection
Xia Lu, Ang Wei, Xu Yang, Jun Liu, Siqi Li, Ying Kan, Wei Wang, Tianyou Wang, Rui Zhang, Jigang Yang
Frontiers in Medicine.2022;[Epub] CrossRef
Prognostic Value of Heterogeneity Index Derived from Baseline 18F-FDG PET/CT in Mantle Cell Lymphoma
Fei Liu, Bingxin Gu, Nan Li, Herong Pan, Wen Chen, Ying Qiao, Shaoli Song, Xiaosheng Liu
Frontiers in Oncology.2022;[Epub] CrossRef
Staging and response assessment of lymphoma: a brief review of the Lugano classification and the role of FDG-PET/CT
Kwai Han Yoo
Blood Research.2022; 57(S1): S75. CrossRef
Prediction of prognosis and pathologic grade in follicular lymphoma using 18F-FDG PET/CT
Hongyan Li, Min Wang, Yajing Zhang, Fan Hu, Kun Wang, Chenyang Wang, Zairong Gao
Frontiers in Oncology.2022;[Epub] CrossRef
PET/CT Evaluation of the Effect of Allogeneic Hematopoietic Stem Cell Transplantation in the Treatment of T‐Cell Lymphoblastic Lymphoma
Jin Zhao, Xiaojing Guo, Li Ma, Meijing Zheng, Tao Guan, Liping Su, Mohammad Farukh Hashmi
Contrast Media & Molecular Imaging.2022;[Epub] CrossRef
Clinical and prognostic role of 2-[18F]FDG PET/CT and sarcopenia in treatment-naïve patients with T-cell lymphoblastic lymphoma
Xiaoyue Tan, Hui Yuan, Dongjiang Li, Xiaolin Sun, Chongyang Ding, Lei Jiang
Annals of Hematology.2022; 101(12): 2699. CrossRef
Prognostic value of baseline total metabolic tumour volume of 18F-FDG PET/CT imaging in patients with angioimmunoblastic T-cell lymphoma
Huanyu Gong, Tiannv Li, Jianyong Li, Lijun Tang, Chongyang Ding
EJNMMI Research.2021;[Epub] CrossRef

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Activation of β₂-Adrenergic Receptor Promotes Growth and Angiogenesis in Breast Cancer by Down-regulating PPARγ: Jing Zhou, Zhanzhao Liu, Lingjing Zhang, Xiao Hu, Zhihua Wang, Hong Ni, Yue Wang, Junfang Qin; Cancer Res Treat. 2020;52(3):830-847. Published online March 4, 2020; DOI: https://doi.org/10.4143/crt.2019.510

Abstract PDF PubReader ePub

Purpose
Chronic stress and related hormones are key in cancer progression. Peroxisome proliferator-activated receptor γ (PPARγ) and its agonists was reported that inducing anti-tumor effect. However, the function of PPARγ in pro-tumorigenic effects induced by chronic stress in breast cancer remains unknown. Herein, we have characterized a novel role of PPARγ and vascular endothelial growth factor (VEGF)/fibroblast growth factor 2 (FGF2) signals in breast cancer promoted by chronic stress.
Materials and Methods
We performed experiments in vivo and in vitro and used bioinformatics data to evaluate the therapeutic potential of PPARγ in breast cancer promoted by stress.
Results
Chronic stress significantly inhibited the PPARγ expression and promoted breast cancer in vivo. VEGF/FGF2-mediated angiogenesis increased in the chronic stress group compared to the control group. PPARγ agonist pioglitazone (PioG) injection offset the pro-tumorigenic effect of chronic stress. Moreover, specific β₂-adrenergic receptor (β₂R) antagonist ICI11-8551 inhibited the effect of chronic stress. In vitro, norepinephrine (NE) treatment had a similar tendency to chronic stress. The effect of NE was mediated by the β₂R/adenylate cyclase signaling pathway and suppressed by PioG. PPARγ suppressed VEGF/FGF2 through reactive oxygen species inhibition. Bioinformatics data confirmed that therewas a lowPPARγ expression in breast invasive carcinoma. Lower PPARγ was associated with a significantly worse survival.
Conclusion
β₂R activation induced by chronic stress and related hormones promotes growth and VEGF/FGF2-mediated angiogenesis of breast cancer by down-regulating PPARγ. Our findings hint that β receptor and PPARγ as two target molecules and the novel role for their agonists or antagonists as clinical medicine in breast cancer therapy

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A Modified NHL-BFM-95 Regimen Produces Better Outcome Than HyperCVAD in Adult Patients with T-Lymphoblastic Lymphoma, a Two-Institution Experience: Chun Li, Zhi-Jun Wuxiao, Xiaoqin Chen, Guanjun Chen, Yue Lu, Zhongjun Xia, Yang Liang, Hua Wang; Cancer Res Treat. 2020;52(2):573-585. Published online December 6, 2019; DOI: https://doi.org/10.4143/crt.2019.542

Abstract PDF Supplementary Material PubReader ePub

Purpose
Lymphoblastic lymphoma (LBL) is an invasive neoplasm of precursor T-cell or B-cell lineage. A broadly accepted standard treatment for adult LBL has not yet been defined.
Materials and Methods
To address this issue, we compared two chemotherapy regimens: a modified non-Hodgkin lymphoma Berlin–Frankfurt–Münster-95 (NHL-BFM-95) regimen and HyperCVAD/MA. This retrospective study consecutively enrolled 207 adult LBL patients at two hospitals from 2000 to 2018. Univariate and multivariate analysis were used to assess prognostic factors.
Results
In the present study, most clinical characteristics were similar between the two treatment groups except for age and lactate dehydrogenase (LDH) level. Patients treated with modified NHL-BFM-95 regimen tended to be younger and with elevated LDH level. The modified NHL-BFM- 95 regimen produced better treatment outcomes than those with HyperCVAD/MA in patients with T-LBL or patients < 40 years. Treatment with HyperCVAD/MA, high Eastern Cooperative Oncology Group scores, and bone marrow involvement were independent risk factors in T-LBL. No patients interrupted treatment for severe adverse events.
Conclusion
The results suggested that the modified regimen is well-tolerated and can produce the promising outcomes in patients with T-LBL or patients < 40 years.

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