A Potent Cancer Vaccine Adjuvant System for Particleization of Short, Synthetic CD8+ T Cell Epitopes.
Xuedan HeShiqi ZhouWei-Chiao HuangAmal SeffouhMoustafa T MabroukM Thomas MorganJoaquin OrtegaScott I AbramsJonathan F LovellPublished in: ACS nano (2021)
Short major histocompatibility complex (MHC) class I (MHC-I)-restricted peptides contain the minimal biochemical information to induce antigen (Ag)-specific CD8+ cytotoxic T cell responses but are generally ineffective in doing so. To address this, we developed a cobalt-porphyrin (CoPoP) liposome vaccine adjuvant system that induces rapid particleization of conventional, short synthetic MHC-I epitopes, leading to strong cellular immune responses at nanogram dosing. Along with CoPoP (to induce particle formation of peptides), synthetic monophosphoryl lipid A (PHAD) and QS-21 immunostimulatory molecules were included in the liposome bilayer to generate the "CPQ" adjuvant system. In mice, immunization with a short MHC-I-restricted peptide, derived from glycoprotein 70 (gp70), admixed with CPQ safely generated functional, Ag-specific CD8+ T cells, resulting in the rejection of multiple tumor cell lines, with durable immunity. When cobalt was omitted, the otherwise identical peptide and adjuvant components did not result in peptide binding and were incapable of inducing immune responses, demonstrating the importance of stable particle formation. Immunization with the liposomal vaccine was well-tolerated and could control local and metastatic disease in a therapeutic setting. Mechanistic studies showed that particle-based peptides were better taken up by antigen-presenting cells, where they were putatively released within endosomes and phagosomes for display on MHC-I surfaces. On the basis of the potency of the approach, the platform was demonstrated as a tool for in vivo epitope screening of peptide microlibraries comprising a hundred peptides.
Keyphrases
- immune response
- early stage
- quantum dots
- induced apoptosis
- squamous cell carcinoma
- amino acid
- small cell lung cancer
- toll like receptor
- metabolic syndrome
- healthcare
- metal organic framework
- dendritic cells
- oxidative stress
- photodynamic therapy
- type diabetes
- transcription factor
- fatty acid
- anti inflammatory
- cell proliferation
- young adults
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- high fat diet induced
- reduced graphene oxide
- inflammatory response
- highly efficient
- lymph node metastasis
- squamous cell
- escherichia coli
- signaling pathway
- social media