Intracellular Bacteria-Mimicking Whole-Cell Cancer Vaccine Potentiates Immune Responses via Concurrent Activation of

Xiaochun Xie1, Zikun Shen1, Yan He2

  • 1School of Medicine, South China University of Technology, Guangzhou, Guangdong 510006, China.

Nano Letters
|June 6, 2025
PubMed

Insights

Engineered whole-cell cancer vaccines mimic bacteria using bimineralization, enhancing immune cell interactions and anti-tumor responses. This novel approach improves vaccine efficacy for melanoma treatment.

Area of Science:

  • Biomaterials Science
  • Immunology
  • Cancer Therapy

Background:

  • Whole-cell cancer vaccines can induce broad anti-tumor immunity but suffer from low immunogenicity and poor antigen-presenting cell (APC) interaction.
  • Developing effective personalized immunotherapies requires overcoming these limitations.

Purpose of the Study:

  • To engineer whole-cell cancer vaccines with enhanced immunogenicity and APC recognition using a novel bimineralization strategy.
  • To investigate the immune response triggered by these engineered cells in a preclinical melanoma model.

Main Methods:

  • Tumor cells were engineered using layer-by-layer bimineralization, combining silicification and manganese mineralization.
  • The resulting bacteria-mimicking cells featured enhanced mechanical stiffness and rough MnO2 nanoclusters.
  • Immune activation was assessed by evaluating NLRP3 inflammasome and cGAS-STING pathway stimulation.

Main Results:

  • Bimineralized tumor cells demonstrated increased mechanical stiffness, protecting antigens from degradation and promoting APC phagocytosis.
  • Manganese mineralization created spiky nanoclusters that effectively stimulated the NLRP3 inflammasome and cGAS-STING pathways.
  • These engineered vaccines showed superior prophylactic and therapeutic effects against B16F10 melanoma in mice compared to monomineralized controls.

Conclusions:

  • Bimineralization is a transformative strategy for creating highly immunogenic whole-cell cancer vaccines.
  • This approach bridges materials science and immunology, offering a new framework for cancer immunotherapy development.

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