Synthesis of multi-antigenic platforms as vaccine candidates against cancers

Cancer cells are characterized by the presence of diverse antigens on their surface. The combination of these structures in a single molecule represents an attractive strategy to obtain vaccine candidates with improved immunological properties. Herein we report the synthesis of a mixture of heterotopic platforms bearing the Tn and TF carbohydrate antigens and an immunostimulating poliovirus peptide.

[1]  R. Roy,et al.  Glycodendrimers as functional antigens and antitumor vaccines , 2012 .

[2]  L. Morelli,et al.  Carbohydrates and Immunology: Synthetic Oligosaccharide Antigens for Vaccine Formulation , 2011 .

[3]  E. Schmitt,et al.  Synthetic antitumor vaccines from tetanus toxoid conjugates of MUC1 glycopeptides with the Thomsen-Friedenreich antigen and a fluorine-substituted analogue. , 2010, Angewandte Chemie.

[4]  A. Nesburn,et al.  Linear and Branched Glyco-Lipopeptide Vaccines Follow Distinct Cross-Presentation Pathways and Generate Different Magnitudes of Antitumor Immunity , 2010, PloS one.

[5]  Zhongwu Guo,et al.  Recent development in carbohydrate-based cancer vaccines. , 2009, Current opinion in chemical biology.

[6]  S. Danishefsky,et al.  A new model for the presentation of tumor-associated antigens and the quest for an anticancer vaccine: a solution to the synthesis challenge via ring-closing metathesis. , 2009, Journal of the American Chemical Society.

[7]  G. Boons,et al.  Immunotherapy for cancer: synthetic carbohydrate-based vaccines. , 2009, Chemical communications.

[8]  F. Bonhomme,et al.  Induction of a Melanoma‐Specific Antibody Response by a Monovalent, but not a Divalent, Synthetic GM2 Neoglycopeptide , 2009, ChemMedChem.

[9]  L. BenMohamed,et al.  Towards a Self‐Adjuvanting Multivalent B and T cell Epitope Containing Synthetic Glycolipopeptide Cancer Vaccine , 2008, ChemMedChem.

[10]  P. Labbé,et al.  Randomized combinatorial library of heteroglycoclusters (hGC). , 2008, Journal of combinatorial chemistry.

[11]  O. Renaudet,et al.  Ethoxyethylidene protecting group prevents N-overacylation in aminooxy peptide synthesis , 2007 .

[12]  M. Wolfert,et al.  Robust immune responses elicited by a fully synthetic three-component vaccine. , 2007, Nature chemical biology.

[13]  A. Delmas,et al.  Synthesis and Biological Evaluation of a Multiantigenic Tn/TF‐Containing Glycopeptide Mimic of the Tumor‐Related MUC1 Glycoprotein , 2006, ChemMedChem.

[14]  H. Kunz,et al.  Synthetic vaccines consisting of tumor-associated MUC1 glycopeptide antigens and bovine serum albumin. , 2005, Angewandte Chemie.

[15]  E. Schmitt,et al.  A fully synthetic vaccine consisting of a tumor-associated glycopeptide antigen and a T-cell epitope for the induction of a highly specific humoral immune response. , 2005, Angewandte Chemie.

[16]  S. Chierici,et al.  Chemoselective assembly and immunological evaluation of multiepitopic glycoconjugates bearing clustered Tn antigen as synthetic anticancer vaccines. , 2005, Bioconjugate chemistry.

[17]  C. Bertozzi,et al.  Glycans in cancer and inflammation — potential for therapeutics and diagnostics , 2005, Nature Reviews Drug Discovery.

[18]  S. Itzkowitz,et al.  Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients , 1995, Cancer Immunology, Immunotherapy.

[19]  S. Danishefsky,et al.  On the power of chemical synthesis: Immunological evaluation of models for multiantigenic carbohydrate-based cancer vaccines , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  W. Bornmann,et al.  Comparison of antibody titers after immunization with monovalent or tetravalent KLH conjugate vaccines. , 2002, Vaccine.

[21]  O. Renaudet,et al.  Expedient synthesis of aminooxylated-carbohydrates for chemoselective access of glycoconjugates , 2001 .

[22]  C. Leclerc,et al.  Anti-Tumor Immunity Provided by a Synthetic Multiple Antigenic Glycopeptide Displaying a Tri-Tn Glycotope1 , 2001, The Journal of Immunology.

[23]  S. Hakomori,et al.  Tumor-associated carbohydrate antigens defining tumor malignancy: basis for development of anti-cancer vaccines. , 2001, Advances in experimental medicine and biology.

[24]  Allen,et al.  From the Laboratory to the Clinic: A Retrospective on Fully Synthetic Carbohydrate-Based Anticancer Vaccines Frequently used abbreviations are listed in the appendix. , 2000, Angewandte Chemie.

[25]  H. Scher,et al.  Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[26]  C. Leclerc,et al.  A fully synthetic immunogen carrying a carcinoma-associated carbohydrate for active specific immunotherapy. , 1999, Cancer research.

[27]  S. Kuduk,et al.  Synthetic and Immunological Studies on Clustered Modes of Mucin-Related Tn and TF O-Linked Antigens: The Preparation of a Glycopeptide-Based Vaccine for Clinical Trials against Prostate Cancer† , 1998 .

[28]  C. Cordon-Cardo,et al.  Selection of tumor antigens as targets for immune attack using immunohistochemistry: I. Focus on gangliosides , 1997, International journal of cancer.

[29]  M. Fukuda.  Possible roles of tumor-associated carbohydrate antigens. , 1996, Cancer research.

[30]  K. Geoghegan,et al.  Site-directed conjugation of nonpeptide groups to peptides and proteins via periodate oxidation of a 2-amino alcohol. Application to modification at N-terminal serine. , 1992, Bioconjugate chemistry.

[31]  T. Feizi,et al.  Carbohydrate structures of glycoproteins and glycolipids as differentiation antigens, tumour-associated antigens and components of receptor systems , 1985 .

[32]  S. Hakomori,et al.  Tumor-associated carbohydrate antigens. , 1984, Annual review of immunology.