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CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity

(2024) BIOMATERIALS. 311.
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Abstract
Cancer vaccines aim at generating cytotoxic CD8+ T cells that kill cancer cells and confer durable tumor regression. Hereto, CD8+ peptide epitopes should be presented by antigen presenting cells to CD8+ T cells in lymphoid tissue. Unfortunately, in unformulated soluble form, peptide antigens are poorly taken up by antigen presenting cells and do not efficiently reach lymph nodes. Hence, the lack of efficient delivery remains a major limitation for successful clinical translation of cancer vaccination using peptide antigens. Here we propose a generic peptide nanoformulation strategy by extending the amino acid sequence of the peptide antigen epitope with 10 glutamic acid residues. The resulting overall anionic charge of the peptide allows encapsulation into lipid nanoparticles (peptide-LNP) by electrostatic interaction with an ionizable cationic lipid. We demonstrate that intravenous injection of peptide-LNP efficiently delivers the peptide to immune cells in the spleen. Peptide-LNP that co-encapsulate an imidazoquinoline TLR7/8 agonist (IMDQ) induce robust innate immune activation in a broad range of immune cell subsets in the spleen. Peptide-LNP containing the minimal CD8+ T cell epitope of the HPV type 16 E7 oncoprotein and IMDQ induces high levels of antigen-specific CD8+ T cells in the blood, and can confer protective immunity against E7-expressing tumors in both prophylactic and therapeutic settings.
Keywords
Vaccines, Cancer immunotherapy, Lipid nanoparticles, Peptides, MHC CLASS-I, DENDRITIC CELLS, T-CELLS, VACCINE, ACTIVATION, INTERFERON, REVEALS, SIGNALS

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MLA
Ye, Tingting, et al. “CO-DELIVERY of Glutamic Acid-Extended Peptide Antigen and Imidazoquinoline TLR7/8 Agonist via Ionizable Lipid Nanoparticles Induces Protective Anti-Tumor Immunity.” BIOMATERIALS, vol. 311, 2024, doi:10.1016/j.biomaterials.2024.122693.
APA
Ye, T., Zhong, Z., Cappellesso, F., Deswarte, K., Chen, Y., Lauwers, H., … De Geest, B. (2024). CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity. BIOMATERIALS, 311. https://doi.org/10.1016/j.biomaterials.2024.122693
Chicago author-date
Ye, Tingting, Zifu Zhong, Federica Cappellesso, Kim Deswarte, Yong Chen, Heleen Lauwers, Emily De Lombaerde, et al. 2024. “CO-DELIVERY of Glutamic Acid-Extended Peptide Antigen and Imidazoquinoline TLR7/8 Agonist via Ionizable Lipid Nanoparticles Induces Protective Anti-Tumor Immunity.” BIOMATERIALS 311. https://doi.org/10.1016/j.biomaterials.2024.122693.
Chicago author-date (all authors)
Ye, Tingting, Zifu Zhong, Federica Cappellesso, Kim Deswarte, Yong Chen, Heleen Lauwers, Emily De Lombaerde, Mark Gontsarik, Stefan Lienenklaus, Dorien Van Lysebetten, Niek Sanders, Bart Lambrecht, Stefaan De Koker, Damya Laoui, and Bruno De Geest. 2024. “CO-DELIVERY of Glutamic Acid-Extended Peptide Antigen and Imidazoquinoline TLR7/8 Agonist via Ionizable Lipid Nanoparticles Induces Protective Anti-Tumor Immunity.” BIOMATERIALS 311. doi:10.1016/j.biomaterials.2024.122693.
Vancouver
1.
Ye T, Zhong Z, Cappellesso F, Deswarte K, Chen Y, Lauwers H, et al. CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity. BIOMATERIALS. 2024;311.
IEEE
[1]
T. Ye et al., “CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity,” BIOMATERIALS, vol. 311, 2024.
@article{01JTNGH0DS8ZGD9Q21C0SS51SG,
  abstract     = {{Cancer vaccines aim at generating cytotoxic CD8+ T cells that kill cancer cells and confer durable tumor regression. Hereto, CD8+ peptide epitopes should be presented by antigen presenting cells to CD8+ T cells in lymphoid tissue. Unfortunately, in unformulated soluble form, peptide antigens are poorly taken up by antigen presenting cells and do not efficiently reach lymph nodes. Hence, the lack of efficient delivery remains a major limitation for successful clinical translation of cancer vaccination using peptide antigens. Here we propose a generic peptide nanoformulation strategy by extending the amino acid sequence of the peptide antigen epitope with 10 glutamic acid residues. The resulting overall anionic charge of the peptide allows encapsulation into lipid nanoparticles (peptide-LNP) by electrostatic interaction with an ionizable cationic lipid. We demonstrate that intravenous injection of peptide-LNP efficiently delivers the peptide to immune cells in the spleen. Peptide-LNP that co-encapsulate an imidazoquinoline TLR7/8 agonist (IMDQ) induce robust innate immune activation in a broad range of immune cell subsets in the spleen. Peptide-LNP containing the minimal CD8+ T cell epitope of the HPV type 16 E7 oncoprotein and IMDQ induces high levels of antigen-specific CD8+ T cells in the blood, and can confer protective immunity against E7-expressing tumors in both prophylactic and therapeutic settings.}},
  articleno    = {{122693}},
  author       = {{Ye, Tingting and Zhong, Zifu and Cappellesso, Federica and Deswarte, Kim and Chen, Yong and Lauwers, Heleen and De Lombaerde, Emily and Gontsarik, Mark and Lienenklaus, Stefan and Van Lysebetten, Dorien and Sanders, Niek and Lambrecht, Bart and De Koker, Stefaan and Laoui, Damya and De Geest, Bruno}},
  issn         = {{0142-9612}},
  journal      = {{BIOMATERIALS}},
  keywords     = {{Vaccines,Cancer immunotherapy,Lipid nanoparticles,Peptides,MHC CLASS-I,DENDRITIC CELLS,T-CELLS,VACCINE,ACTIVATION,INTERFERON,REVEALS,SIGNALS}},
  language     = {{eng}},
  pages        = {{18}},
  title        = {{CO-DELIVERY of glutamic acid-extended peptide antigen and imidazoquinoline TLR7/8 agonist via ionizable lipid nanoparticles induces protective anti-tumor immunity}},
  url          = {{http://doi.org/10.1016/j.biomaterials.2024.122693}},
  volume       = {{311}},
  year         = {{2024}},
}

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