Team led by Professors Jin-Hong Wi and Wan-Wook Kim at Catholic University College of Medicine: Nanovaccine, Anticancer Chemotherapy, and Immune Checkpoint Clues presented to overcome 'anticancer drug resistance' through inhibitor combination 

-Triple combination therapy inhibits the growth of resistant tumors and blocks recurrence after surgery-

[Photo] Professor Jin-Hong Wi, Department of Physiology, Catholic University of Korea College of Medicine, and Professor Wan-Wook Kim, Department of Rheumatology, Seoul St. Mary's Hospital (Co-corresponding authors) 

 A research team led by Professor Jin-Hong Wi of the Department of Physiology, Catholic University College of Medicine and Professor Wan-Wook Kim of the Department of Rheumatology, Seoul St. Mary's Hospital, has proposed a new combination therapy strategy that can overcome chemotherapy resistance and suppress tumor recurrence after surgery. 

 Chemotherapy for solid tumors faces limitations, such as cancer cells acquiring drug resistance during repeated administration and frequent recurrence caused by residual cancer cells even after surgery. This acquired resistance and recurrence have been identified as key factors limiting the long-term efficacy of conventional anticancer treatments, and the development of new treatment strategies to overcome these challenges has been pointed out as an urgent task. 

 The research team developed a novel combination anticancer therapy strategy combining a cancer nanovaccine with the anticancer drug doxorubicin and the immune checkpoint inhibitor anti-PD-L1 to simultaneously suppress anticancer drug resistance and cancer recurrence after surgery. The cancer nanovaccine developed by the team consists of biodegradable PLGA nanoparticles loaded with the tumor-specific antigen HPV E7 peptide and the adjuvant poly I:C. This nanovaccine promoted the maturation of dendritic cells and enhanced the CD8⁺ cytotoxic T-cell immune response, which selectively attacks tumor cells. 

 In animal models of tumors resistant to doxorubicin, triple combination therapy with nanovaccine, doxorubicin, and anti-PD-L1 effectively inhibited tumor growth compared to monotherapy. Furthermore, it increased intratumoral CD8⁺ T-cell infiltration and tumor-specific immune responses, while simultaneously reducing the proliferation of immunosuppressive cells and tumor cells, as well as angiogenesis. 

 In particular, combination therapy reduced the expression of MDR1 (ABCB1), a resistance protein involved in anticancer drug elimination, and the CD44⁺CD133⁺ cancer stem cell-like cell population. This demonstrates the potential to not only reduce tumor size but also mitigate the anticancer drug resistance characteristics of the tumor itself. Through results showing a significant decrease in these therapeutic effects when CD8⁺ T cells were removed, the research team also confirmed that CD8⁺ T cells play a key role in tumor suppression and the alleviation of anticancer drug resistance.

 In a postoperative recurrence model, no tumor recurrence occurred in the triple combination therapy group during the observation period, and it was confirmed that effector memory T cells involved in long-term immune defense also increased. No significant toxicity was observed in liver and kidney function or major organ tissues after the administration of the nanovaccine, confirming its potential in terms of safety. 

 "This study is significant in that it presents preclinical evidence that cancer nanovaccines can simultaneously enhance the effects of anticancer chemotherapy and immune checkpoint inhibitors, thereby controlling drug-resistant tumors and suppressing recurrence after surgery," said Professor Wi Jin-hong. "It is expected to develop into a new combination immunotherapy strategy for the treatment of drug-resistant solid tumors through further verification using various tumor models and human-derived tumors in the future." 

 This study was published in the international academic journal Journal of Nanobiotechnology (IF=15), with Professor Young-Min Park of Sejong University (Director of the National Drug Development Center, lead corresponding author), Dr. Dae-Kyun Jeong of the Korea Research Institute of Bioscience and Biotechnology, and Dr. Hee-Dong Han of Prestige Biopharma participating as co-corresponding authors. 

[Figure 1]

Left (A): Structure of the cancer nanovaccine developed by the research team.

Right (B): Action process of the triple combination therapy involving the cancer nanovaccine, anticancer drug, and immunotherapy drug.