Preparation and Immunological Evaluation of Nanoparticulate Self-adjuvanting Peptide Vaccines as  Breast Cancer Vaccine Candidates — ASN Events
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  3. Preparation and Immunological Evaluation of Nanoparticulate Self-adjuvanting Peptide Vaccines as  Breast Cancer Vaccine Candidates

Preparation and Immunological Evaluation of Nanoparticulate Self-adjuvanting Peptide Vaccines as  Breast Cancer Vaccine Candidates (#263)

Keita Ito 1 , Yoshiyuki Manabe 1 2 , Hiroto Furukawa 3 , Hiroshi Inaba 3 4 , Kazunori Matsuura 3 4 , Masatoshi Maeki 5 , Manabu Tokeshi 5 , Shino Ohshima 6 , Yoshie Kametani 6 , Kazuya Kabayama 1 2 , Koichi Fukase 1 2
  1. Graduate School of Science, Osaka University, Toyonaka, Osaka, Japan
  2. Forefront Research Center, Osaka University, Toyonaka, Osaka, Japan
  3. Graduate School of Engineering, Tottori University, Tottori, Japan
  4. Center for Research on Green Sustainable Chemistry, Tottori University, Tottori, Japan
  5. Faculty of Engineering, Hokkaido University, Sapporo, Hokkaido, Japan
  6. School of Medicine, Tokai University, Isehara, Kanagawa, Japan

Peptide-based cancer vaccines hold a significant promise as a modality of cancer immunotherapy. However, peptide antigens often suffer from low immunogenicity, impeding their practical application. To overcome this drawback, self-adjuvanting vaccines, which are the conjugate/co-assembly of antigens with immunostimulatory adjuvants, have recently garnered significant attention. The important aspects of self-adjuvanting vaccines are the induction of antigen-specific immune responses through the co-delivery of antigens and adjuvants to the same immune cells, or the presentation of multivalent antigens. Inspired by these properties of self-adjuvanting vaccines, we herein designed two nanoparticulate self-adjuvanting vaccines.

The first vaccine, “lipid nanoparticle (LNP) vaccines”, consists of cationic LNPs that encapsulate both the lipidated peptide antigen (CH401 peptide, breast cancer antigen) and adjuvants (Pam3CSK4, α-GalCer, MPLA, and CpG ODN). We also prepared the LNP vaccine incorporating the conjugate of Pam3CSK4 and CH401 peptide. These LNP vaccines were prepared using microfluidic device “iLiNP”, which enables the formulation of size-controlled LNPs (<100 nm).

The second vaccine, “enveloped viral replica vaccine”, is cationic-bilayer enveloped artificial viral capsid self-assembled from β-annulus peptide, which forms the capsid skeleton of tomato-bushy-stunt virus. We introduced the CH401 peptide antigen at C-terminus of the β-annulus and incorporated a lipophilic adjuvant (α-GalCer) into the lipid envelope.

These nanoparticulate self-adjuvanting vaccines possess favorable physiological properties (<100 nm, spherical), facilitating efficient co-delivery of antigen and adjuvant to lymph nodes and their uptake to dendritic cells. The LNP vaccines and the enveloped viral replica vaccine showed efficient induction of CH401-specific antibody in vivo, demonstrating the potential of nanoparticulate self-adjuvanting vaccines as promising tools for cancer immunotherapy.

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