- Breast cancer
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Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study
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Ruyan Zhang, Xiaoran Liu, Guohong Song, Yan Zhang, Huiping Li
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Cancer Res Treat. 2024;56(3):795-801. Published online December 20, 2023
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DOI: https://doi.org/10.4143/crt.2023.1151
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 Abstract
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- Purpose
This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) after progression of trastuzumab.
Materials and Methods
In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of trastuzumab received pertuzuamb, HLX02, and chemotherapy in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495).
Results
A total of 45 patients were included in this study. Twelve patients (26.7%) were treated in second-line and 33 patients (73.3%) were in third-line and later setting. Eighty percent and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range, 1.2 to 43.9 months), the median PFS was 7.6 months (95% confidence interval, 4.3 to 10.9), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated.
Conclusion
The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond-line treatment in HER2-positive MBC.
- General
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Engineering a High-Affinity PD-1 Peptide for Optimized Immune Cell-Mediated Tumor Therapy
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Yilei Chen, Hongxing Huang, Yin Liu, Zhanghao Wang, Lili Wang, Quanxiao Wang, Yan Zhang, Hua Wang
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Cancer Res Treat. 2022;54(2):362-374. Published online August 3, 2021
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DOI: https://doi.org/10.4143/crt.2021.424
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Abstract
PDF
 Supplementary MaterialPubReaderePub
- 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, KD=11.9 nM) for PD-1 was obtained by optimizing the nABP284 peptide (KD=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.
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Citations
Citations to this article as recorded by  - 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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