Antitumor activity of a self-adjuvanting glyco-lipopeptide vaccine bearing B cell, CD4+ and CD8+ T cell epitopes

  • Ilham Bettahi
  • Gargi Dasgupta
  • Olivier Renaudet
  • Aziz Alami Chentoufi
  • Xiuli Zhang
  • Dale Carpenter
  • Susan Yoon
  • Pascal Dumy
  • Lbachir BenMohamedEmail author
Original Article


Molecularly defined synthetic vaccines capable of inducing both antibodies and cellular anti-tumor immune responses, in a manner compatible with human delivery, are limited. Few molecules achieve this target without utilizing external immuno-adjuvants. In this study, we explored a self-adjuvanting glyco-lipopeptide (GLP) as a platform for cancer vaccines using as a model MO5, an OVA-expressing mouse B16 melanoma. A prototype B and T cell epitope-based GLP molecule was constructed by synthesizing a chimeric peptide made of a CD8+ T cell epitope, from ovalbumin (OVA257–264) and an universal CD4+ T helper (Th) epitope (PADRE). The resulting CTL–Th peptide backbones was coupled to a carbohydrate B cell epitope based on a regioselectively addressable functionalized templates (RAFT), made of four α-GalNAc molecules at C-terminal. The N terminus of the resulting glycopeptides (GP) was then linked to a palmitic acid moiety (PAM), obviating the need for potentially toxic external immuno-adjuvants. The final prototype OVA-GLP molecule, delivered in adjuvant-free PBS, in mice induced: (1) robust RAFT-specific IgG/IgM that recognized tumor cell lines; (2) local and systemic OVA257–264-specific IFN-γ producing CD8+ T cells; (3) PADRE-specific CD4+ T cells; (4) OVA-GLP vaccination elicited a reduction of tumor size in mice inoculated with syngeneic murine MO5 carcinoma cells and a protection from lethal carcinoma cell challenge; (5) finally, OVA-GLP immunization significantly inhibited the growth of pre-established MO5 tumors. Our results suggest self-adjuvanting glyco-lipopeptide molecules as a platform for B Cell, CD4+, and CD8+ T cell epitopes-based immunotherapeutic cancer vaccines.


Vaccine Carbohydrate Glyco-lipopeptide CD4+ T cell CD8+ T cell 



This work was supported by NIH Grants EY14900, EY16663, The Discovery Eye Foundation Research to Prevent Blindness, Unrestricted Challenge Grant (LBM) and by the Centre National pour la Recherche Scientifique (CNRS), the Université Joseph Fourier (UJF), and the COST D-34 (DP).


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ilham Bettahi
    • 1
  • Gargi Dasgupta
    • 1
  • Olivier Renaudet
    • 2
  • Aziz Alami Chentoufi
    • 1
  • Xiuli Zhang
    • 1
  • Dale Carpenter
    • 1
  • Susan Yoon
    • 1
  • Pascal Dumy
    • 2
  • Lbachir BenMohamed
    • 1
    • 3
    Email author
  1. 1.Laboratory of Cellular and Molecular Immunology, The Gavin S. Herbert Eye InstituteUniversity of California Irvine, College of MedicineIrvine, OrangeUSA
  2. 2.Département de Chimie Moléculaire, UMR-CNRS 5250, ICMG FR 2607Universite Joseph FourierGrenoble Cedex 9France
  3. 3.Center for ImmunologyUniversity of California IrvineIrvineUSA

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