Theranostics · 2026
Ganglioside enhances the immunogenicity of nanoparticles displaying short synthetic tumor neoepitopes and epitopes.
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Zhou Shiqi, Luo Yuan, Twilhaar Maarten K Nijen, Huang Wei-Chiao, Seffouh Amal, Song Yiting, Su Yafei, Quinn Breandan, Wu Yun, Neelamegham Sriram, Ortega Joaquin, den Haan Joke M M, Lovell Jonathan F
Аннотация
RATIONALE: Short major histocompatibility class I epitopes can be coupled to the surface of immunogenic liposomes to elicit antigen-specific CD8+ T cells with vaccination. Here, we examined whether the co-incorporation of GM3 ganglioside, a lipid which targets CD169, a sialic acid-binding receptor, would further improve the immunogenicity of this approach.
METHODS: Liposomes were formed with GM3 incorporated and were assessed for CD169 targeting and anti-tumor immunogenicity in murine models. Antigen-specific CD8+ T cell populations and characteristics were investigated to examine the effect of liposome formulations.
RESULTS: GM3 was readily incorporated into immunogenic liposomes and did not interfere with the particle formation with a recently discovered murine renal carcinoma MHC-I neoepitope, Nes2LR. GM3 enhanced the CD169 targeting of liposomes. Immunization with liposomal particles that included GM3 improved antigen-specific CD8+ T cell responses for not only the Nes2LR neoepitope, but for other tumor-associated short MHC-I murine tumor epitopes or mimotopes, including E749-57, and the gp70 mimotope AH1-A5. Immunization of the E7 epitope with GM3 particles induced high-frequency E7-specific CD8+ T cells and effectively reversed the tumor growth of large, established TC-1 tumors as an immune monotherapy. Immunization of the Nes2LR neoepitope in GM3 particles led to delayed tumor growth of RENCA tumors.
CONCLUSION: GM3 ganglioside-containing liposomes that display short peptide epitopes and incorporate immunological adjuvants can be used to elicit potent anti-tumor responses in murine models. Further research is required to further assess the translational potential of this approach.
METHODS: Liposomes were formed with GM3 incorporated and were assessed for CD169 targeting and anti-tumor immunogenicity in murine models. Antigen-specific CD8+ T cell populations and characteristics were investigated to examine the effect of liposome formulations.
RESULTS: GM3 was readily incorporated into immunogenic liposomes and did not interfere with the particle formation with a recently discovered murine renal carcinoma MHC-I neoepitope, Nes2LR. GM3 enhanced the CD169 targeting of liposomes. Immunization with liposomal particles that included GM3 improved antigen-specific CD8+ T cell responses for not only the Nes2LR neoepitope, but for other tumor-associated short MHC-I murine tumor epitopes or mimotopes, including E749-57, and the gp70 mimotope AH1-A5. Immunization of the E7 epitope with GM3 particles induced high-frequency E7-specific CD8+ T cells and effectively reversed the tumor growth of large, established TC-1 tumors as an immune monotherapy. Immunization of the Nes2LR neoepitope in GM3 particles led to delayed tumor growth of RENCA tumors.
CONCLUSION: GM3 ganglioside-containing liposomes that display short peptide epitopes and incorporate immunological adjuvants can be used to elicit potent anti-tumor responses in murine models. Further research is required to further assess the translational potential of this approach.