Academic Journal
Anti-PD-1/CTLA-4 bispecific antibody-based combination therapy for cervical cancer: a multicenter study with biomarker analysis.
| Τίτλος: | Anti-PD-1/CTLA-4 bispecific antibody-based combination therapy for cervical cancer: a multicenter study with biomarker analysis. |
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| Συγγραφείς: | Li J; Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China., Deng Y; Department of Gynecologic Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Hunan Cancer Hospital, Central South University, Changsha, China., Wu T; Department of Oncology, Changde Hospital, Xiangya School of Medicine, Changde, China., Xu C; Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China., Zou W; Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China., Yao J; Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, China., Wang J; Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China. |
| Πηγή: | Frontiers in immunology [Front Immunol] 2026 Oct 01; Vol. 17, pp. 1967065. Date of Electronic Publication: 2026 Oct 01 (Print Publication: 2026). |
| Τύπος έκδοσης: | Journal Article; Multicenter Study |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| Ιατρικοί όροι (MeSH): | Uterine Cervical Neoplasms*/drug therapy , Uterine Cervical Neoplasms*/mortality , Uterine Cervical Neoplasms*/immunology , Uterine Cervical Neoplasms*/genetics , Uterine Cervical Neoplasms*/pathology , Antibodies, Bispecific*/therapeutic use , Antibodies, Bispecific*/adverse effects , Antibodies, Bispecific*/administration & dosage , Biomarkers, Tumor*/genetics , Programmed Cell Death 1 Receptor*/antagonists & inhibitors , Programmed Cell Death 1 Receptor*/immunology , CTLA-4 Antigen*/antagonists & inhibitors , CTLA-4 Antigen*/immunology , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use , Antineoplastic Combined Chemotherapy Protocols*/adverse effects , Immune Checkpoint Inhibitors*/therapeutic use , Immune Checkpoint Inhibitors*/adverse effects, Humans ; Female ; Retrospective Studies ; Middle Aged ; Adult ; Treatment Outcome ; Aged |
| Περίληψη: | Background: Cadonilimab is a PD-1/CTLA-4 bispecific antibody with robust activity in platinum-pretreated advanced cervical cancer, while its first-line value and resistance mechanisms remain unclear. Methods: This multicenter retrospective study enrolled 52 treatment-naive patients with recurrent/metastatic cervical cancer (R/M CC) receiving cadonilimab plus chemotherapy. We assessed clinical efficacy and safety, and performed RNA-seq and immunohistochemistry for exploratory biomarker analysis. Results: The 2-year overall survival, 2-year progression-free survival and objective response rate were 82.6%, 66.7% and 75.0%, respectively. Main treatment-related adverse events included myelosuppression, thyroid dysfunction, gastrointestinal reactions and fatigue, demonstrating acceptable safety. Transcriptomic data showed suppressed Hippo, NF-κB, RIG-1 pathways and reduced M1-macrophage polarization in patients with longer PFS. Candidate genes including GGT6 and FRG2 were identified as putative resistance-associated markers in this small exploratory cohort. Higher M1-macrophage polarization and p-STAT1 expression were observed in short-PFS patients, indicating a possible link between p-STAT1 activation and M1-macrophage enrichment. Of note, outcomes should be interpreted considering the retrospective single-arm design and limited sample size. Conclusions: Cadonilimab-containing regimen achieved promising efficacy and an acceptable safety profile as first-line therapy for R/M CC. The biomarker findings are exploratory and provide preliminary evidence for future research on bispecific-antibody resistance. (Copyright © 2026 Li, Deng, Wu, Xu, Zou, Yao and Wang.) |
| Competing Interests: | The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| Contributed Indexing: | Keywords: RNA sequence; biomarkers; cervical cancer; immunotherapy; resistance |
| Substance Nomenclature: | 0 (Antibodies, Bispecific) 0 (Biomarkers, Tumor) 0 (Programmed Cell Death 1 Receptor) 0 (CTLA-4 Antigen) 0 (PDCD1 protein, human) 0 (Immune Checkpoint Inhibitors) 0 (CTLA4 protein, human) |
| Entry Date(s): | Date Created: 20261017 Date Completed: 20261017 Latest Revision: 20261017 |
| Update Code: | 20261018 |
| PubMed Central ID: | PMC13669150 |
| DOI: | 10.3389/fimmu.2026.1967065 |
| PMID: | 42889160 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2026.1967065 |