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Xiao Wu1, Yifeng Tan1, Jing Zhang1
1College of Biomedical Engineering and National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China. szhang@scu.edu.cn.
Abstract:
Immunogenic cell death (ICD) induced by reactive oxygen species (ROS) represents a particular form of tumor cell death for approaching the problem of low immunogenicity of tumors in immunotherapy, while the oxidative damage to normal cells of current ICD inducers hinders their clinical application. Herein, a new ICD inducer VC@cLAV constructed solely by dietary antioxidants, lipoic acid (LA) and vitamin C (VC), is developed, which could promote heavy intracellular ROS production in cancer cells for ICD induction while acting as an anti-oxidant in non-cancer cells for cytoprotection, and thus hold high biosafety. In vitro studies show that VC@cLAV induced a release of antigens and a maturation rate of DCs up to 56.5%, approaching the positive control (58.4%). In vivo combined with αPD-1, VC@cLAV showed excellent antitumor activity against both primary and distant metastatic tumors with an inhibition rate of 84.8% and 79.0% compared to 14.2% and 10.0% in the αPD-1 alone group. Notably, VC@cLAV established a long-term antitumor immune memory effect against tumor rechallenging. This study not only presents a new kind of ICD inducer but also provides an impetus for the development of dietary antioxidant-based cancer drugs.
Insights
A novel immunogenic cell death (ICD) inducer, VC@cLAV, made from dietary antioxidants, effectively targets cancer cells for immunotherapy while protecting normal cells. This approach enhances antitumor immune memory and offers a safer alternative for cancer treatment.
Area of Science:
- Oncology
- Immunotherapy
- Nanomedicine
Background:
- Tumor cells often exhibit low immunogenicity, posing challenges for effective cancer immunotherapy.
- Current inducers of immunogenic cell death (ICD) can cause oxidative damage to normal cells, limiting their clinical use.
- Reactive oxygen species (ROS) play a crucial role in inducing ICD.
Purpose of the Study:
- To develop a novel ICD inducer with high biosafety for cancer immunotherapy.
- To investigate the potential of using dietary antioxidants for cancer treatment.
- To create an ICD inducer that selectively targets cancer cells while protecting normal cells.
Main Methods:
- Development of VC@cLAV, a novel ICD inducer composed of lipoic acid (LA) and vitamin C (VC).
- In vitro assessment of VC@cLAV's ability to induce antigen release and dendritic cell (DC) maturation.
- In vivo evaluation of VC@cLAV's antitumor efficacy, both alone and in combination with αPD-1 therapy, in mouse models.
- Assessment of long-term antitumor immune memory following VC@cLAV treatment.
Main Results:
- VC@cLAV demonstrated significant antigen release and DC maturation in vitro (56.5% vs. 58.4% for positive control).
- In vivo studies showed substantial tumor inhibition rates (84.8% for primary, 79.0% for metastatic tumors) when combined with αPD-1, significantly outperforming αPD-1 alone (14.2% and 10.0%).
- VC@cLAV established a durable antitumor immune memory effect, protecting against tumor rechallenging.
Conclusions:
- VC@cLAV is a novel, safe, and effective ICD inducer derived from dietary antioxidants.
- This agent selectively induces ROS in cancer cells for ICD while offering antioxidant protection to normal cells.
- VC@cLAV holds significant promise for developing advanced, antioxidant-based cancer therapeutics and immunotherapy strategies.
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