In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular Carcinoma
Ja-Der Liang,1 Po-Chin Liang,2,3 Chia-Tung Shun,4 Chien-Hung Chen,1,5 Yao-Ming Wu,6,7 Yu-Chen Hsu,4,8 Ying-Te Lee,4 Pei-Ming Yang,1,4 Guan-Tarn Huang,1,9 Andres M Salazar,10 Hsuan-Shu Lee,1,4 Jin-Chuan Sheu,1,4 Meng-Tzu Weng1,11 1Department of Internal Medicine, National Taiwan University Hospital a...
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Dove Medical Press
2025-06-01
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| Series: | Journal of Hepatocellular Carcinoma |
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| Online Access: | https://www.dovepress.com/in-situ-vaccination-with-poly-iclc-combined-with-systemic-nivolumab-fo-peer-reviewed-fulltext-article-JHC |
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| author | Liang JD Liang PC Shun CT Chen CH Wu YM Hsu YC Lee YT Yang PM Huang GT Salazar AM Lee HS Sheu JC Weng MT |
| author_facet | Liang JD Liang PC Shun CT Chen CH Wu YM Hsu YC Lee YT Yang PM Huang GT Salazar AM Lee HS Sheu JC Weng MT |
| author_sort | Liang JD |
| collection | DOAJ |
| description | Ja-Der Liang,1 Po-Chin Liang,2,3 Chia-Tung Shun,4 Chien-Hung Chen,1,5 Yao-Ming Wu,6,7 Yu-Chen Hsu,4,8 Ying-Te Lee,4 Pei-Ming Yang,1,4 Guan-Tarn Huang,1,9 Andres M Salazar,10 Hsuan-Shu Lee,1,4 Jin-Chuan Sheu,1,4 Meng-Tzu Weng1,11 1Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 2Department of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 3Department of Medical Imaging, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan; 4Liver Disease Prevention and Treatment Research Foundation, Taipei, Taiwan; 5Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; 6Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 7Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; 8Department of Clinical Laboratory Science and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; 9Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 10Oncovir, Washington, DC, USA; 11Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, TaiwanCorrespondence: Meng-Tzu Weng, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan, Tel +886-2-23123456 ext 67266, Fax +886-2-23947927, Email G05157@hch.gov.twPurpose: Unresectable hepatocellular carcinoma (HCC) presents significant therapeutic challenges. While immune checkpoint inhibitors (ICIs) are part of the current standard of care, combining poly-ICLC as an in situ vaccination with an ICI may enhance treatment efficacy. The study investigated the safety and therapeutic effects of combining poly-ICLC with nivolumab, an ICI, in patients with unresectable HCC.Patients and Methods: Patients with unresectable HCC were enrolled to receive intratumoral and intramuscular poly-ICLC injections along in combination with nivolumab infusions. The primary endpoint was safety, and secondary endpoints included objective response as measured by mRECIST and changes in serum alpha-fetoprotein (AFP) levels. Gene expression profiling, pathway analysis, and immune cell type deconvolution were conducted using NanoString GeoMx Digital Spatial Profiling.Results: Four patients were enrolled. The combination therapy was safe and well-tolerated. Among them, one patient achieved a complete response (CR), and another achieved a partial response (PR). Both responders showed significant declines in serum AFP levels. Notably, the patient with CR showed eradication of cancerous component of the portal vein thrombus, and an abscopal effect was observed in the patient with PR. Gene analysis indicated that interferon-gamma signaling was the most enriched pathway in tumors of the responders.Conclusion: This combination therapy was safe and effective, with two out of four patients demonstrating objective responses. These preliminary findings warrant further investigation into larger clinical cohorts.Keywords: Hepatocellular carcinoma, Poly-ICLC, In situ vaccination, immune checkpoint inhibitors, Portal vein thrombus, Digital spatial profiling |
| format | Article |
| id | doaj-art-c3329f84a2c743cd9fa2e4220bc2ced2 |
| institution | Matheson Library |
| issn | 2253-5969 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Journal of Hepatocellular Carcinoma |
| spelling | doaj-art-c3329f84a2c743cd9fa2e4220bc2ced22025-06-25T21:33:51ZengDove Medical PressJournal of Hepatocellular Carcinoma2253-59692025-06-01Volume 12Issue 111911204103906In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular CarcinomaLiang JD0Liang PC1Shun CT2Chen CH3Wu YM4Hsu YCLee YTYang PMHuang GT5Salazar AMLee HS6Sheu JCWeng MT7Department of Internal Medicine,Medical Image Dept.Depat Of Pathology and Forensic Medicine, National Taiwan University HospitalDepartment of Internal MedicineSurgeryInternal MedicineInternal MedicineInternal MedicineJa-Der Liang,1 Po-Chin Liang,2,3 Chia-Tung Shun,4 Chien-Hung Chen,1,5 Yao-Ming Wu,6,7 Yu-Chen Hsu,4,8 Ying-Te Lee,4 Pei-Ming Yang,1,4 Guan-Tarn Huang,1,9 Andres M Salazar,10 Hsuan-Shu Lee,1,4 Jin-Chuan Sheu,1,4 Meng-Tzu Weng1,11 1Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 2Department of Medical Imaging and Radiology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 3Department of Medical Imaging, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan; 4Liver Disease Prevention and Treatment Research Foundation, Taipei, Taiwan; 5Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; 6Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 7Department of Surgical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan; 8Department of Clinical Laboratory Science and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; 9Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 10Oncovir, Washington, DC, USA; 11Department of Medical Research, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, TaiwanCorrespondence: Meng-Tzu Weng, Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan, Tel +886-2-23123456 ext 67266, Fax +886-2-23947927, Email G05157@hch.gov.twPurpose: Unresectable hepatocellular carcinoma (HCC) presents significant therapeutic challenges. While immune checkpoint inhibitors (ICIs) are part of the current standard of care, combining poly-ICLC as an in situ vaccination with an ICI may enhance treatment efficacy. The study investigated the safety and therapeutic effects of combining poly-ICLC with nivolumab, an ICI, in patients with unresectable HCC.Patients and Methods: Patients with unresectable HCC were enrolled to receive intratumoral and intramuscular poly-ICLC injections along in combination with nivolumab infusions. The primary endpoint was safety, and secondary endpoints included objective response as measured by mRECIST and changes in serum alpha-fetoprotein (AFP) levels. Gene expression profiling, pathway analysis, and immune cell type deconvolution were conducted using NanoString GeoMx Digital Spatial Profiling.Results: Four patients were enrolled. The combination therapy was safe and well-tolerated. Among them, one patient achieved a complete response (CR), and another achieved a partial response (PR). Both responders showed significant declines in serum AFP levels. Notably, the patient with CR showed eradication of cancerous component of the portal vein thrombus, and an abscopal effect was observed in the patient with PR. Gene analysis indicated that interferon-gamma signaling was the most enriched pathway in tumors of the responders.Conclusion: This combination therapy was safe and effective, with two out of four patients demonstrating objective responses. These preliminary findings warrant further investigation into larger clinical cohorts.Keywords: Hepatocellular carcinoma, Poly-ICLC, In situ vaccination, immune checkpoint inhibitors, Portal vein thrombus, Digital spatial profilinghttps://www.dovepress.com/in-situ-vaccination-with-poly-iclc-combined-with-systemic-nivolumab-fo-peer-reviewed-fulltext-article-JHCHepatocellular carcinomaPoly-ICLCIn situ vaccinationimmune checkpoint inhibitorsPortal vein thrombusDigital spatial profiling. |
| spellingShingle | Liang JD Liang PC Shun CT Chen CH Wu YM Hsu YC Lee YT Yang PM Huang GT Salazar AM Lee HS Sheu JC Weng MT In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular Carcinoma Journal of Hepatocellular Carcinoma Hepatocellular carcinoma Poly-ICLC In situ vaccination immune checkpoint inhibitors Portal vein thrombus Digital spatial profiling. |
| title | In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular Carcinoma |
| title_full | In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular Carcinoma |
| title_fullStr | In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular Carcinoma |
| title_full_unstemmed | In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular Carcinoma |
| title_short | In Situ Vaccination with Poly-ICLC Combined with Systemic Nivolumab for the Treatment of Unresectable Hepatocellular Carcinoma |
| title_sort | in situ vaccination with poly iclc combined with systemic nivolumab for the treatment of unresectable hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Poly-ICLC In situ vaccination immune checkpoint inhibitors Portal vein thrombus Digital spatial profiling. |
| url | https://www.dovepress.com/in-situ-vaccination-with-poly-iclc-combined-with-systemic-nivolumab-fo-peer-reviewed-fulltext-article-JHC |
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