GM3 ganglioside and α-galactosylceramide incorporation in liposomes results in uptake by CD169+ macrophages, iNKT cell activation and potent adaptive immunity

Grabowska, J. (Speaker)

Activity: Talk or presentationOral presentation

Description

Successful anti-cancer vaccines aim to prime and/or reinvigorate cytotoxic T cells and therefore should comprise potent antigen and adjuvant. Antigen targeting to splenic CD169+ macrophages has been shown to induce robust CD8+ T cell responses which were dependent on antigen transfer to cDC1. α-galactosylceramide (aGC) is known to act as a strong adjuvant by stimulation of invariant natural killer T (iNKT) cells. Here we evaluated the immune activating capacity of liposomes that contain the CD169 ligand ganglioside GM3, aGC, and ovalbumin (OVA) protein. Systemically administered GM3-aGC-OVA liposomes were specifically taken up by splenic CD169+ macrophages and stimulated cytokine production by iNKT cells and cDC1 maturation 16 h post injection. Strong OVA-specific CD8+ T cell and B cell responses were detected 7 days after immunization with GM3-aGC-OVA liposomes. CD8+ T cell, but not iNKT and B cell, responses were dependent on the presence of CD169+ macrophages and cDC1. In summary, our results suggest that GM3-aGC-antigen liposomes provide a strong combination of targeting ligand and adjuvant that promotes the interaction between different splenic immune cell populations resulting in activation of adaptive immunity and therefore emerge as an interesting anti-cancer vaccination platform.
Period10 Dec 2020
Event titleNVVI annual meeting
Event typeConference
Degree of RecognitionNational