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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Engineered Outer Membrane Vesicles as Nanosized Immune Cell Engagers for Enhanced Solid Tumor Immunotherapy.

Jianan Sun1, Liu Tan1, Bang-Ce Ye2

  • 1Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

ACS Nano
|October 25, 2024
PubMed
Summary

Researchers developed a novel OMV-based immune cell engager (OMV-NICE) for solid tumor immunotherapy. This dual-targeting approach enhances immune cell engagement and demonstrates superior antitumor activity in preclinical models.

Keywords:
SpyCatcher/SnoopCatcherimmune cell engagernanobodyouter membrane vesiclestumor immunotherapy

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Area of Science:

  • Immunology
  • Biotechnology
  • Nanomedicine

Background:

  • Solid tumors present significant challenges for current tumor immunotherapies.
  • Developing effective strategies to engage immune cells against solid tumors is crucial.

Purpose of the Study:

  • To engineer an OMV-based nanosized immune cell engager (OMV-NICE) for enhanced solid tumor immunotherapy.
  • To investigate the dual-targeting capabilities of OMV-NICE against CD47/SIRPα and PD-1/PD-L1 pathways.

Main Methods:

  • Utilized bacterial outer membrane vesicles (OMVs) as scaffolds for nanobody conjugation.
  • Employed orthogonal SpyCatcher-SpyTag and SnoopCatcher-SnoopTag chemistries for dual and trivalent nanobody attachment.
  • Evaluated OMV-NICE efficacy through in vitro assays (macrophage phagocytosis, T cell cytotoxicity) and in vivo studies in a B16-F10 melanoma mouse model.

Main Results:

  • Confirmed functional retention of nanobodies on OMV-NICE, showing synergistic enhancement of immune cell functions.
  • Demonstrated superior in vivo antitumor activity of OMV-NICE compared to unconjugated nanobodies and OMVs alone.
  • Mechanistic studies revealed enhanced recruitment of macrophages and T cells to the tumor site by OMV-NICE.

Conclusions:

  • The developed OMV-NICE platform offers a promising new approach for solid tumor immunotherapy.
  • OMV-NICE effectively engages immune cells and exhibits potent antitumor effects, expanding the repertoire of immune cell engagers.