Biomimetic Glyconanoparticle Vaccine for Cancer Immunotherapy

Eliran Moshe Reuven, Shani Leviatan Ben-Arye, Hai Yu, Roberto Duchi, Andrea Perota, Sophie Conchon, Shirley Bachar Abramovitch, Jean Paul Soulillou, Cesare Galli, Xi Chen, Vered Padler-Karavani

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Cancer immunotherapy aims to harness the immune system to combat malignant processes. Transformed cells harbor diverse modifications that lead to formation of neoantigens, including aberrantly expressed cell surface carbohydrates. Targeting tumor-associated carbohydrate antigens (TACA) hold great potential for cancer immunotherapy. N-glycolylneuraminic acid (Neu5Gc) is a dietary non-human immunogenic carbohydrate that accumulates on human cancer cells, thereby generating neoantigens. In mice, passive immunotherapy with anti-Neu5Gc antibodies inhibits growth of Neu5Gc-positive tumors. Here, we designed an active cancer vaccine immunotherapy strategy to target Neu5Gc-positive tumors. We generated biomimetic glyconanoparticles using engineered αGal knockout porcine red blood cells to form nanoghosts (NGs) that either express (NG pos ) or lack expression (NG neg ) of Neu5Gc-glycoconjugates in their natural context. We demonstrated that optimized immunization of "human-like" Neu5Gc-deficient Cmah -/- mice with NG pos glyconanoparticles induce a strong, diverse and persistent anti-Neu5Gc IgG immune response. The resulting anti-Neu5Gc IgG antibodies were also detected within Neu5Gc-positive tumors and inhibited tumor growth in vivo. Using detailed glycan microarray analysis, we further demonstrate that the kinetics and quality of the immune responses influence the efficacy of the vaccine. These findings reinforce the potential of TACA neoantigens and the dietary non-human sialic acid Neu5Gc, in particular, as immunotherapy targets.

Original languageEnglish (US)
Pages (from-to)2936-2947
Number of pages12
JournalACS Nano
Volume13
Issue number3
DOIs
StatePublished - Mar 26 2019

Keywords

  • biomimetic
  • cancer immunotherapy
  • glycan microarray
  • glyconanoparticle
  • N-glycolylneuraminic acid
  • neoantigen
  • sialic acid

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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  • Cite this

    Reuven, E. M., Leviatan Ben-Arye, S., Yu, H., Duchi, R., Perota, A., Conchon, S., Bachar Abramovitch, S., Soulillou, J. P., Galli, C., Chen, X., & Padler-Karavani, V. (2019). Biomimetic Glyconanoparticle Vaccine for Cancer Immunotherapy. ACS Nano, 13(3), 2936-2947. https://doi.org/10.1021/acsnano.8b07241