Cancer nanovaccine plus doxorubicin and immune checkpoint blockade overcomes chemoresistance and delays postsurgical recurrence
9 affiliations
- 1Department of Integrative Biological Sciences and Industry, College of Life Science, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea
- 2Tumor immunology lab (TIL), College of Health Sciences, Dong-A University, 37 Nakdong-daero 550beon-gil, Saha-gu, Busan, Republic of Korea
- 3Innovative Discovery Center, Prestige Biopharma, 164 Myeongjigukje 6- ro, Busan, Republic of Korea
- 4Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea
- 5Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 6Department of Medical Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 7Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University of Korea, Seoul, Republic of Korea
- 8Department of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of Korea
- 9Division of Rheumatology, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
Abstract
Chemotherapy for solid tumors has serious limitations due to acquired chemoresistance and frequent postsurgical recurrence. In this study, we developed a chemo-immunotherapy regimen combining a chemotherapeutic agent, a dendritic cell (DC)-activating cancer nanovaccine, and immune checkpoint blockade (ICB) to overcome chemoresistance and improve long-term tumor control. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles co-encapsulating a tumor-specific antigen (HPV E7 peptide) and an adjuvant (poly I:C), termed PLGA (E7 + poly I:C)-NPs, were engineered as the nanovaccine platform. PLGA (E7 + poly I:C)-NPs promoted DC maturation and induced pro-inflammatory cytokine production. In a doxorubicin (DOX)-resistant tumor model, co-administration of PLGA (E7 + poly I:C)-NPs, DOX, and anti-PD-L1 antibody significantly reduced tumor burden, decreased tumor cell proliferation, and lowered microvessel density. This combination therapy also synergistically enhanced cytotoxic CD8⁺ T cell responses in both the spleen and tumor and delayed postsurgical recurrence, consistent with an increased effector memory T cell population. Moreover, MDR1 (ABCB1) expression was downregulated and the CD44⁺CD133⁺ cancer stem-like cell fraction was reduced, supporting reversal of chemoresistant features. Collectively, these findings demonstrate that integrating a cancer nanovaccine with chemotherapy and PD-L1 blockade can enhance antitumor immunity, overcome chemoresistance, and delay recurrence in chemoresistant tumors. This approach offers the potential to improve therapeutic outcomes and prolong survival in patients with various chemoresistant tumors.
Graphical Abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12951-026-04892-3.
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BibTeX
@article{lee2026cancer,
title = {{Cancer nanovaccine plus doxorubicin and immune checkpoint blockade overcomes chemoresistance and delays postsurgical recurrence}},
author = {Chan Mi Lee and Yun Kyeong Kwon and Ji Eun Won and Jae Hee Lee and Dae Gwin Jeong and Jinhong Wie and Wan-Uk Kim and Hee Dong Han and Yeong-Min Park},
journal = {Journal of Nanobiotechnology},
year = {2026},
month = aug,
doi = {10.1186/s12951-026-04892-3},
url = {https://doi.org/10.1186/s12951-026-04892-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Cancer nanovaccine plus doxorubicin and immune checkpoint blockade overcomes chemoresistance and delays postsurgical recurrence
AU - Chan Mi Lee
AU - Yun Kyeong Kwon
AU - Ji Eun Won
AU - Jae Hee Lee
AU - Dae Gwin Jeong
AU - Jinhong Wie
AU - Wan-Uk Kim
AU - Hee Dong Han
AU - Yeong-Min Park
PY - 2026
DA - 2026/08/07
JO - Journal of Nanobiotechnology
DO - 10.1186/s12951-026-04892-3
UR - https://doi.org/10.1186/s12951-026-04892-3
AB - Chemotherapy for solid tumors has serious limitations due to acquired chemoresistance and frequent postsurgical recurrence. In this study, we developed a chemo-immunotherapy regimen combining a chemotherapeutic agent, a dendritic cell (DC)-activating cancer nanovaccine, and immune checkpoint blockade (ICB) to overcome chemoresistance and improve long-term tumor control. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles co-encapsulating a tumor-specific antigen (HPV E7 peptide) and an adjuvant (poly I:C), termed PLGA (E7 + poly I:C)-NPs, were engineered as the nanovaccine platform. PLGA (E7 + poly I:C)-NPs promoted DC maturation and induced pro-inflammatory cytokine production. In a doxorubicin (DOX)-resistant tumor model, co-administration of PLGA (E7 + poly I:C)-NPs, DOX, and anti-PD-L1 antibody significantly reduced tumor burden, decreased tumor cell proliferation, and lowered microvessel density. This combination therapy also synergistically enhanced cytotoxic CD8⁺ T cell responses in both the spleen and tumor and delayed postsurgical recurrence, consistent with an increased effector memory T cell population. Moreover, MDR1 (ABCB1) expression was downregulated and the CD44⁺CD133⁺ cancer stem-like cell fraction was reduced, supporting reversal of chemoresistant features. Collectively, these findings demonstrate that integrating a cancer nanovaccine with chemotherapy and PD-L1 blockade can enhance antitumor immunity, overcome chemoresistance, and delay recurrence in chemoresistant tumors. This approach offers the potential to improve therapeutic outcomes and prolong survival in patients with various chemoresistant tumors. Graphical Abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12951-026-04892-3.
SN - 1477-3155
ER -