Genetically Programmable Fusion Cellular Vesicles for Cancer Immunotherapy

Abstract

Herein, we report that genetically programmable fusion cellular vesicles (Fus‐CVs) displaying high‐affinity SIRPα variants and PD‐1 can activate potent antitumor immunity through both innate and adaptive immune effectors. Dual‐blockade of CD47 and PD‐L1 with Fus‐CVs significantly increases the phagocytosis of cancer cells by macrophages, promotes antigen presentation, and activates antitumor T‐cell immunity. Moreover, the bispecific targeting design of Fus‐CVs ensures better targeting on tumor cells, but less on other cells, which reduces systemic side effects and enhances therapeutic efficacies. In malignant melanoma and mammary carcinoma models, we demonstrate that Fus‐CVs significantly improve overall survival of model animals by inhibiting post‐surgery tumor recurrence and metastasis. The Fus‐CVs are suitable for protein display by genetic engineering. These advantages, integrated with other unique properties inherited from source cells, make Fus‐CVs an attractive platform for multi‐targeting immune checkpoint blockade therapy.

Biomimetic manganese-based theranostic nanoplatform for cancer multimodal imaging and twofold immunotherapy

“…Western blot was performed as previously described [ 29 ]. Briefly, the samples were lysed 1 × SDS-PAGE loading buffer and then the lysates were resolved by SDS-PAGE and transferred to polyvinylidene difluoride (PVDF) membranes.…”

“…Based on the peculiarity of gold, manganese nanomaterials and our previous biomimetic engineering experiences [ 25 , 26 ], we firstly constructed composite nanoparticles of MnO 2 coating gold nanorod (GNR) with the help of silicon dioxide (SiO 2 ). Then, the composite nanoparticles GNR@SiO 2 @MnO 2 (hereafter referred to as GSM) was coated myeloid-derived suppressor cells (MDSCs) membrane, which can actively target TME [ 27 ], to construct the ultimate multi-functional nano-theranostics agent (GNR@SiO 2 @MnO 2 @MDSCs, hereafter referred to as GSMM) ( Scheme 1 ).…”

Recent Progress of Exosome Isolation and Peptide Recognition-Guided Strategies for Exosome Research

“…Since the first clinical trial in the treatment of metastatic melanoma patients ( Escudier et al, 2005 ), exosomes have attracted more and more attention in the field of drug delivery and disease treatment ( Meng et al, 2021 ; Xie et al, 2021 ). As a platform for drug delivery and disease treatment, exosomes have several significant advantages.…”

Role of CD47-SIRPα Checkpoint in Nanomedicine-Based Anti-Cancer Treatment

“…CD47 sends a “don’t eat me” signal to the innate immune system, inhibiting the phagocytosis of macrophages by engaging SIRPα ( Hayat et al, 2020 ; Logtenberg et al, 2020 ; Zhang et al, 2020 ). Hence, dual-blockade of PD-L1 and CD47 can activate potent antitumor effects via both innate and adaptive immune responses ( Chen et al, 2019c ; Lian et al, 2019 ; Meng et al, 2021 ; Pham et al, 2021 ; Zhao et al, 2021 ). For example, Meng et al designed genetically programmable fusion cellular vesicles (Fus-CVs), which were fused by SIRPα variants and PD-1 variants.…”