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In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
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Genetically Programmable Fusion Cellular Vesicles for Cancer Immunotherapy

Qian-Fang Meng1, Yuyue Zhao2, Chunbo Dong3

  • 1Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China.

Angewandte Chemie (International Ed. in English)
|October 18, 2021
PubMed

Insights

Genetically engineered fusion cellular vesicles (Fus-CVs) activate potent antitumor immunity by blocking CD47 and PD-L1. This dual-blockade enhances cancer cell phagocytosis and T-cell responses, improving survival in preclinical models.

Area of Science:

  • Immunology
  • Biotechnology
  • Oncology

Background:

  • Cancer immunotherapy aims to harness the immune system against tumors.
  • Immune checkpoints like CD47 and PD-L1 regulate immune responses and are often exploited by cancer cells.
  • Developing targeted therapies that overcome immune evasion is crucial for effective cancer treatment.

Purpose of the Study:

  • To engineer fusion cellular vesicles (Fus-CVs) for dual blockade of CD47 and PD-L1.
  • To evaluate the efficacy of Fus-CVs in activating innate and adaptive antitumor immunity.
  • To assess the therapeutic potential of Fus-CVs in preclinical cancer models.

Main Methods:

  • Genetic engineering of cellular vesicles to display high-affinity SIRPα variants and PD-1.
  • In vitro assessment of macrophage phagocytosis and antigen presentation.
  • In vivo studies in malignant melanoma and mammary carcinoma models to evaluate tumor recurrence, metastasis, and survival.

Main Results:

  • Fus-CVs effectively blocked CD47 and PD-L1, significantly increasing cancer cell phagocytosis by macrophages.
  • Dual blockade activated antitumor T-cell immunity and promoted antigen presentation.
  • Treatment with Fus-CVs significantly improved overall survival by inhibiting post-surgery tumor recurrence and metastasis in preclinical models.

Conclusions:

  • Genetically programmable Fus-CVs represent a promising platform for multi-targeting immune checkpoint blockade therapy.
  • The bispecific targeting of Fus-CVs enhances therapeutic efficacy while minimizing systemic side effects.
  • Fus-CVs demonstrate significant potential for improving outcomes in various cancer types.
Keywords:
CD47/SIRPαPD-1/PD-L1cell membrane nanoparticlegenetic engineeringimmune checkpoint therapy

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