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Published on: May 22, 2020
MnO2-melittin nanoparticles serve as an effective anti-tumor immunotherapy by enhancing systemic immune response
Shupei Tang1, Lan Zhou2, Haiyang He2
1Department of Urology, Daping Hospital, Third Military Medical University, Chongqing, 400042, China.
Abstract:
Cancer vaccines are viewed as a promising immunotherapy to eradicate malignant tumors and aim to elicit the patients' own tumor-specific immune response against tumor cells. However, few cancer vaccines have been applied due to the low immunogenicity of antigen and invalidation of adjuvant. Herein, we designed a tumor microenvironment (TME) responsive MnO2-melittin nanoparticles (M-M NPs). The M-M NPs consumed glutathione and produced •OH via Fenton-like reaction in the mimic TME, specifically caused tumor cell death in vitro, activated cGAS-STING pathway in vitro and promoted the maturation of antigen-presenting cells in vitro and in vivo to elicit systemic anti-tumor immune response including the augmentation of tumor-specific T cells and more productions of pro-inflammatory cytokines and chemokines, which all were stronger than MnO2 NPs and melittin. The anti-tumor effects of M-M NPs were evaluated in three subcutaneous tumor models and the B16-F10 lung metastasis model and the tumor growth and lung metastasis were more obviously inhibited in the M-M NPs treated mice, compared with MnO2 NPs and melittin treatments. More importantly, only M-M NPs promoted the MHC-I cross-dressing by dendritic cells to prime tumor-specific CD8+ T cells and remarkably suppressed the growth of left tumors if express cognate antigen while treating on the right in the bilateral tumor model. Our findings proposed a strategy to enhance the cancer vaccine efficiency which showed great therapeutic effect on tumor immunotherapy.
Insights
This study introduces novel manganese dioxide-melittin nanoparticles (M-M NPs) that effectively target the tumor microenvironment. These nanoparticles enhance anti-tumor immunity and significantly inhibit tumor growth and metastasis, offering a promising cancer vaccine strategy.
Area of Science:
- Immunology
- Nanotechnology
- Oncology
Background:
- Cancer vaccines are a promising immunotherapy but face challenges due to low antigen immunogenicity and adjuvant ineffectiveness.
- Developing strategies to overcome these limitations is crucial for advancing cancer immunotherapy.
- The tumor microenvironment (TME) presents unique challenges and opportunities for therapeutic intervention.
Purpose of the Study:
- To design and evaluate tumor microenvironment (TME)-responsive manganese dioxide-melittin nanoparticles (M-M NPs) as a cancer vaccine.
- To assess the M-M NPs' ability to enhance anti-tumor immune responses and therapeutic efficacy.
- To investigate the mechanism of M-M NPs in priming tumor-specific T cells and suppressing tumor growth.
Main Methods:
- Fabrication of M-M NPs utilizing manganese dioxide (MnO2) and melittin, designed for TME responsiveness.
- In vitro evaluation of M-M NPs for glutathione consumption, reactive oxygen species (ROS) production, tumor cell death, and immune pathway activation (cGAS-STING).
- In vivo assessment of M-M NPs in subcutaneous and metastatic tumor models, including analysis of immune cell populations, cytokine profiles, and MHC-I cross-dressing.
Main Results:
- M-M NPs effectively consumed glutathione and produced hydroxyl radicals (•OH) in a mimic TME, leading to enhanced tumor cell death and cGAS-STING pathway activation.
- M-M NPs significantly promoted antigen-presenting cell maturation, augmented tumor-specific T cells, and increased pro-inflammatory cytokine/chemokine production compared to controls.
- M-M NPs demonstrated superior inhibition of tumor growth and lung metastasis in vivo and induced MHC-I cross-dressing in dendritic cells to prime CD8+ T cells.
Conclusions:
- M-M NPs represent a novel strategy to enhance cancer vaccine efficiency by leveraging TME-responsive properties.
- The designed nanoparticles effectively elicit a systemic anti-tumor immune response and exhibit significant therapeutic effects.
- This approach shows great potential for improving cancer immunotherapy outcomes, particularly in overcoming immune evasion mechanisms.
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01:27Tumor Immunotherapy
02:17The Tumor Microenvironment