Multifunctional Bispecific Nanovesicles Targeting SLAMF7 Trigger Potent Antitumor Immunity

Area of Science:

• Immunology
• Nanotechnology
• Oncology

Background:

• Immune checkpoint inhibitor (ICI) therapy efficacy is limited by poor cytotoxic T cell infiltration and an immunosuppressive tumor microenvironment (TME).
• Signaling lymphocytic activation molecule family member 7 (SLAMF7) is a co-stimulatory receptor that can activate NK cells, T cells, and macrophages against tumors.
• The therapeutic potential of SLAMF7 in solid tumors is limited by its expression solely on hematopoietic cells.

Purpose of the Study:

• To develop and characterize multifunctional bispecific nanovesicles (NVs) targeting SLAMF7 and glypican-3 (GPC3), a hepatocellular carcinoma (HCC)-specific antigen.
• To investigate the capacity of these NVs to induce antitumor immunity and remodel the TME.

Main Methods:

• Development of bispecific nanovesicles (NVs) engineered to target both SLAMF7 and GPC3.
• Characterization of NV targeting efficiency and their impact on the tumor microenvironment.
• Assessment of NV-induced antitumor immunity and synergy with PD1 blockade.

Main Results:

• The developed NVs effectively decorated solid tumor surfaces by targeting SLAMF7 and GPC3.
• Targeting SLAMF7 with NVs induced potent and specific antitumor immune responses.
• The NVs remodeled the immunosuppressive TME and sensitized tumors to programmed cell death protein 1 (PD1) blockade.

Conclusions:

• Multifunctional bispecific NVs targeting SLAMF7 represent a promising strategy to enhance antitumor immunity.
• This approach effectively overcomes TME-mediated suppression and synergizes with existing immunotherapies like PD1 blockade.
• These findings have implications for developing next-generation targeted cancer therapies, particularly for HCC.