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Antigenic Liposomes for Generation of Disease-specific Antibodies
Published on: October 25, 2018
Anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) for adoptive cell
Chunxiong Zheng1, Qingguo Zhong1, Ke Yi1
1Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Abstract:
Equipping multiple functionalities on adoptive effector cells is essential to overcome the complex immunological barriers in solid tumors for superior antitumor efficacy. However, current cell engineering technologies cannot endow these functionalities to cells within a single step because of the different spatial distributions of targets in one cell. Here, we present a core-shell anti-phagocytosis-blocking repolarization-resistant membrane-fusogenic liposome (ARMFUL) to achieve one-step multiplexing cell engineering for multifunctional cell construction. Through fusing with the M1 macrophage membrane, ARMFUL inserts an anti-CD47 (aCD47)-modified lipid shell onto the surface and simultaneously delivers colony-stimulating factor 1 receptor inhibitor BLZ945-loaded core into the cytoplasm. The surface-presenting aCD47 boosts macrophage's phagocytosis against the tumor by blocking CD47. The cytoplasm-located BLZ945 prompts its polarization resistance to M2 phenotype in the immunosuppressive microenvironment via inactivating the intracellular M2 polarization signaling pathway. This ARMFUL provides a versatile cell engineering platform to customize multimodal cellular functions for enhanced adoptive cell therapy.
Insights
This study introduces a novel liposome (ARMFUL) for one-step cell engineering. ARMFUL enhances adoptive cell therapy by equipping effector cells with multiple tumor-fighting functions, improving antitumor efficacy.
Area of Science:
- Biotechnology
- Immunology
- Nanomedicine
Background:
- Solid tumors present complex immunological barriers that limit the efficacy of adoptive cell therapy.
- Current cell engineering methods struggle to equip effector cells with multiple functionalities simultaneously due to target spatial distribution.
Purpose of the Study:
- To develop a one-step cell engineering platform for constructing multifunctional effector cells.
- To overcome limitations in current cell engineering technologies for enhanced adoptive cell therapy.
Main Methods:
- A core-shell, membrane-fusogenic liposome (ARMFUL) was designed for one-step multiplexing cell engineering.
- ARMFUL fuses with M1 macrophage membranes, delivering an anti-CD47 (aCD47) modified shell and a BLZ945-loaded core into the cytoplasm.
- The aCD47 blocks CD47 to enhance phagocytosis, while BLZ945 inhibits M2 polarization in the immunosuppressive tumor microenvironment.
Main Results:
- ARMFUL successfully engineered multifunctional cells in a single step.
- Surface aCD47 enhanced tumor phagocytosis by blocking CD47-mediated signaling.
- Cytoplasmic BLZ945 conferred resistance to M2 polarization, maintaining effector cell function.
Conclusions:
- ARMFUL serves as a versatile platform for engineering multifunctional cells for adoptive cell therapy.
- This approach enhances antitumor efficacy by overcoming immunological barriers in solid tumors.
- The technology offers a novel strategy for customizing cellular functions to improve therapeutic outcomes.
