{"title":"Targeting CD30L in B-cell non-Hodgkin lymphoma: novel peptide conjugates and their therapeutic potential.","authors":"Chaowen Shi, Tianzheng Lan, Yufeng Gao, Zhiquan Liang, Yafei Zhang, Yanbei Tu, Hanqing Liu, Zhigang Tu","doi":"10.1186/s12943-025-02393-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>B-cell non-Hodgkin lymphoma (B-NHL) constitutes the majority of NHL cases. Patients with B-NHL often experience multiple recurrences, necessitating several lines of antitumor therapy, and develop drug resistance. The recent success of therapeutic strategies targeting CD19 and CD20 highlights the therapeutic potential of identifying unique molecular markers in B-NHL for precision medicine, although challenges like immunogenicity and limited tumor penetration persist.</p><p><strong>Methods: </strong>In this study, whole-cell phage display was employed to identify the specific binding peptide TG-1 towards B-NHL cells which was confirmed in vitro and in vivo, and its corresponding target CD30 ligand (CD30L) was identified by mass spectrometry and validated by functional assays, molecular docking, bioinformational analyses, knockdown, and rescue experiments. Additionally, the effects of TG-1 and functional roles of CD30L in B-NHL cells were investigated by exploring the molecular mechanisms of CD30/CD30L interactions. Furthermore, TG-1 peptide and doxorubicin co-functionalized gold nanoparticles (AuNPs) were characterized, and their effects on B-NHL cell proliferation were studied both in vitro and in vivo.</p><p><strong>Results: </strong>Here, we identified and validated the CD30L as a novel target on B-NHL cells, along with its highly specific binding peptide TG-1, using whole-cell phage display. TG-1 binds CD30L, impairing lymphoma cell viability by disrupting the CD30-CD30L signaling axis, which is crucial for B-NHL cell survival. It demonstrates strong inhibitory effects on lymphoma cell proliferation both in vitro and in vivo. Additionally, the peptide and doxorubicin co-functionalized AuNPs demonstrated significant inhibitory effects on B-NHL cell proliferation, highlighting their potential as a promising therapeutic strategy.</p><p><strong>Conclusions: </strong>In summary, our findings underscore the potential of CD30L as a novel target for B-NHL treatment and demonstrate the promise of CD30L-targeted peptides in advancing precision medicine for B-NHL, paving the way for future clinical developments.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"24 1","pages":"189"},"PeriodicalIF":27.7000,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12943-025-02393-9","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: B-cell non-Hodgkin lymphoma (B-NHL) constitutes the majority of NHL cases. Patients with B-NHL often experience multiple recurrences, necessitating several lines of antitumor therapy, and develop drug resistance. The recent success of therapeutic strategies targeting CD19 and CD20 highlights the therapeutic potential of identifying unique molecular markers in B-NHL for precision medicine, although challenges like immunogenicity and limited tumor penetration persist.
Methods: In this study, whole-cell phage display was employed to identify the specific binding peptide TG-1 towards B-NHL cells which was confirmed in vitro and in vivo, and its corresponding target CD30 ligand (CD30L) was identified by mass spectrometry and validated by functional assays, molecular docking, bioinformational analyses, knockdown, and rescue experiments. Additionally, the effects of TG-1 and functional roles of CD30L in B-NHL cells were investigated by exploring the molecular mechanisms of CD30/CD30L interactions. Furthermore, TG-1 peptide and doxorubicin co-functionalized gold nanoparticles (AuNPs) were characterized, and their effects on B-NHL cell proliferation were studied both in vitro and in vivo.
Results: Here, we identified and validated the CD30L as a novel target on B-NHL cells, along with its highly specific binding peptide TG-1, using whole-cell phage display. TG-1 binds CD30L, impairing lymphoma cell viability by disrupting the CD30-CD30L signaling axis, which is crucial for B-NHL cell survival. It demonstrates strong inhibitory effects on lymphoma cell proliferation both in vitro and in vivo. Additionally, the peptide and doxorubicin co-functionalized AuNPs demonstrated significant inhibitory effects on B-NHL cell proliferation, highlighting their potential as a promising therapeutic strategy.
Conclusions: In summary, our findings underscore the potential of CD30L as a novel target for B-NHL treatment and demonstrate the promise of CD30L-targeted peptides in advancing precision medicine for B-NHL, paving the way for future clinical developments.
期刊介绍:
Molecular Cancer is a platform that encourages the exchange of ideas and discoveries in the field of cancer research, particularly focusing on the molecular aspects. Our goal is to facilitate discussions and provide insights into various areas of cancer and related biomedical science. We welcome articles from basic, translational, and clinical research that contribute to the advancement of understanding, prevention, diagnosis, and treatment of cancer.
The scope of topics covered in Molecular Cancer is diverse and inclusive. These include, but are not limited to, cell and tumor biology, angiogenesis, utilizing animal models, understanding metastasis, exploring cancer antigens and the immune response, investigating cellular signaling and molecular biology, examining epidemiology, genetic and molecular profiling of cancer, identifying molecular targets, studying cancer stem cells, exploring DNA damage and repair mechanisms, analyzing cell cycle regulation, investigating apoptosis, exploring molecular virology, and evaluating vaccine and antibody-based cancer therapies.
Molecular Cancer serves as an important platform for sharing exciting discoveries in cancer-related research. It offers an unparalleled opportunity to communicate information to both specialists and the general public. The online presence of Molecular Cancer enables immediate publication of accepted articles and facilitates the presentation of large datasets and supplementary information. This ensures that new research is efficiently and rapidly disseminated to the scientific community.