Hybrid Vesicles Based on Autologous Tumor Cell Membrane and Bacterial Outer Membrane To Enhance Innate Immune Response and Personalized Tumor Immunotherapy

Abstract

Tumor heterogeneity, often leading to metastasis, limits the development of tumor therapy. Personalized therapy is promising to address tumor heterogeneity. Here, a vesicle system was designed to enhance innate immune response and amplify personalized immunotherapy. Briefly, the bacterial outer membrane vesicle (OMV) was hybridized with the cell membrane originated from the tumor (mT) to form new functional vesicles (mTOMV). In vitro experiments revealed that the mTOMV strengthened the activation of innate immune cells and increased the specific lysis ability of T cells in homogeneous tumors. In vivo experiments showed that the mTOMV effectively accumulated in inguinal lymph nodes, then inhibited lung metastasis. Besides, the mTOMV evoked adaptive immune response in homologous tumor rather than the heterogeneous tumor, reversibly demonstrating the effects of personalized immunotherapy. The functions to inhibit tumor growth and metastasis accompanying good biocompatibility and simple preparation procedure of mTOMV provide their great potential for clinical applications.

Construction of Nanocarriers Based on Endogenous Cell Membrane and Their Application in Nanomedicine

“…Over the last few years, EMBNs have been widely developed as powerful systems for drug delivery. [ 22 ] After extracting cell membranes in different ways, the NPs are wrapped with different cell membranes, so that the physical characteristics and unique functions of the cell are preserved. These strategies successfully avoid the scavenging effects of MPS and the RES on the NPs, increase the circulation time of the anticancer drugs, and allow the NPs to specifically bind to tumor sites and perform the typical functions of the different cells.…”

Cell Membrane-Derived Vesicle: A Novel Vehicle for Cancer Immunotherapy

“…Researchers constructed fusion vesicles by hybridizing E. coli outer membrane vesicles and tumor cell vesicles in order to simultaneously augment innate and adaptive immunity for personalized tumor immunotherapy. The fusion vesicles could be effectively enriched in lymph nodes and inhibited the growth and lung metastasis of colorectal and breast tumors ( 57 ). In another similar study, tumor cell membrane and E. coli cytomembrane were co-extruded with nanoparticles to obtain hybrid vaccine.…”

Tumor-Derived Membrane Vesicles: A Promising Tool for Personalized Immunotherapy

“…In addition, loading indocyanine green (ICG) inside the hybrid vesicles can induce local photothermal effects, effectively destroying solid tumors and inhibiting tumor recurrence. Zuo et al constructed hybrid vesicles fused with E. coli membranes and TCMVs to inhibit tumor metastasis ( Figure 3 ) [ 191 ]. Due to the immunogenicity of bacterial membranes, hybrid vesicles are more likely to be accumulated in the draining lymph nodes than single TCMVs.…”

“…( D ) Bilateral tumor model to validate the effect of fusion vesicle personalized immunotherapy. Reproduced with permission [ 191 ]. Copyright 2021, American Chemical Society.…”