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한빛사논문
- 조회135
J. Immunother. Cancer, Mar 21 2025, 13 (3) e010272 | https://doi.org/10.1136/jitc-2024-010272
Thermoresistant flagellin-adjuvanted cancer vaccine combined with photothermal therapy synergizes with anti-PD-1 treatment
Jayalakshmi Thiruppathi,1 Veena Vijayan,1 Hye Suk Hwang,1,2 Yong Jun Bang,1 Vandara Loeurng,1 Seol Hee Hong,3 Aravindkumar Sundaram,1 In-Kyu Park,4 Shee Eun Lee,3 Joon Haeng Rhee1
1Chonnam National University, Hwasun, Korea (the Republic of)
2Department of Biomedical Science,College of Life Science and Industry, Sunchon National University, Sunchon 57922, South Korea
3Chonnam National University, Gwangju, Korea (the Republic of)
4Chonnam National University Medical School, Gwangju, Korea (the Republic of)
Correspondence to
Professor Joon Haeng Rhee; Professor Shee Eun Lee; Professor In-Kyu Park
1Chonnam National University, Hwasun, Korea (the Republic of)
2Department of Biomedical Science,College of Life Science and Industry, Sunchon National University, Sunchon 57922, South Korea
3Chonnam National University, Gwangju, Korea (the Republic of)
4Chonnam National University Medical School, Gwangju, Korea (the Republic of)
Correspondence to
Professor Joon Haeng Rhee; Professor Shee Eun Lee; Professor In-Kyu Park
Abstract
Background: Cancer immunotherapy, leveraging the immune system to target and eradicate cancer cells, has transformed cancer treatment paradigms. Immune checkpoint inhibitors (ICIs) are used in a wide array of cancers, but only a limited fraction of patients are responding. Cancer vaccines could elicit antigen-specific immune responses and establish long-term immune memory, preventing recurrence and metastasis. Despite their promising profiles, ICIs and cancer vaccines by themselves are often insufficient to overcome the immunosuppressive tumor microenvironment (TME) and recurrence/metastasis. Addressing these challenges is crucial for improving cancer immunotherapy outcomes.
Methods: The targeted liposomal formulation (TLIF), displaying Cyclic RGD (cRGD) peptide on the surface and encapsulating ICG and thermoresistant flagellin (FlaB) inside, was used for photothermal therapy (PTT), which was designed to induce robust immunogenic cell death (ICD) and release tumor antigens (TAs). We employed a mouse breast cancer model amenable to PTT. Utilizing a bilateral DD-Her2/neu tumor implantation model, we evaluated local and abscopal effects of combinatorial approaches employing PTT, FlaB-adjuvanted peptide vaccine (FlaB-Vax), and anti-PD-1 treatment. FlaB-Vax was designed to trigger tumor-associated antigen (TAA)-specific immune responses, which will trigger specific anti-tumor immunity. TLIF-PTT aimed to reduce tumor burden and induce ICD-mediated TA liberation for epitope spreading. Sustained anti-tumor immune memory was assessed by orthotopic rechallenging cured mice with the DD-Her2/neu tumor cells.
Results: The combination of TLIF-PTT and FlaB-Vax provided significantly enhanced primary tumor suppression, with strong abscopal effects and long-lasting immune memory. The addition of anti-PD-1 therapy further improved long-term relapse-free survival, highlighting the potential of this combinatorial approach to induce durable antitumor immunity and sustainably prevent cancer recurrence and metastasis.
Conclusion: This study demonstrates that the combination of TLIF-PTT and FlaB-Vax synergistically induced synergistic anti-tumor immune responses, which were efficaciously potentiated by anti-PD-1 treatment for recurrence-free long-term survival.
Methods: The targeted liposomal formulation (TLIF), displaying Cyclic RGD (cRGD) peptide on the surface and encapsulating ICG and thermoresistant flagellin (FlaB) inside, was used for photothermal therapy (PTT), which was designed to induce robust immunogenic cell death (ICD) and release tumor antigens (TAs). We employed a mouse breast cancer model amenable to PTT. Utilizing a bilateral DD-Her2/neu tumor implantation model, we evaluated local and abscopal effects of combinatorial approaches employing PTT, FlaB-adjuvanted peptide vaccine (FlaB-Vax), and anti-PD-1 treatment. FlaB-Vax was designed to trigger tumor-associated antigen (TAA)-specific immune responses, which will trigger specific anti-tumor immunity. TLIF-PTT aimed to reduce tumor burden and induce ICD-mediated TA liberation for epitope spreading. Sustained anti-tumor immune memory was assessed by orthotopic rechallenging cured mice with the DD-Her2/neu tumor cells.
Results: The combination of TLIF-PTT and FlaB-Vax provided significantly enhanced primary tumor suppression, with strong abscopal effects and long-lasting immune memory. The addition of anti-PD-1 therapy further improved long-term relapse-free survival, highlighting the potential of this combinatorial approach to induce durable antitumor immunity and sustainably prevent cancer recurrence and metastasis.
Conclusion: This study demonstrates that the combination of TLIF-PTT and FlaB-Vax synergistically induced synergistic anti-tumor immune responses, which were efficaciously potentiated by anti-PD-1 treatment for recurrence-free long-term survival.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-24)
- 국내 연구진
- 의약학 > 면역의학
관련 보도자료
혁신적 암 면역치료법 개발… 광열치료·항암 백신·면역관문억제제 병합으로 종양 제거 및 재발 방지
전남대학교 이준행·이시은·박인규 교수 연구팀이 새로운 암면역치료법을 개발하여 미국 암면역치료학회 공식 학회지인 ‘Journal for Immunotherapy of Cancer’에 게재했다고 밝혔다. 현재 다양한 암면역치료법이 개발되어 임상에 적용되고 있지만, 어떤 강력한 면역치료제든 단독치료만으로는 모든 환자들에서 암을 완벽하게 제어하기 어렵다는 암면역치료법의 한계도 서서히 자각되고 있는 상황에서 대안으로서 2가지 이상의 치료법을 전략적으로 혼합 적용하는 복합암면역치료가 떠오르고 있다.
- Bio통신원
- 2025. 03. 31
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