From synthesis to biologics: preclinical data on a chemistry derived anticancer vaccine.

Abstract	A fully synthetic anticancer vaccine 2 has been prepared via bioconjugation of unimolecular pentavalent construct 1-containing five prostate and breast cancer associated carbohydrate antigens, Globo-H, GM2, STn, TF and Tn-to maleimide-modified carrier protein KLH. An improved conjugation protocol has been developed, which allowed us to obtain a higher epitope ratio of the unimolecular pentavalent glycopeptide antigen to the carrier protein (505/1 versus 228/1 for the previous version). KLH conjugate 2 has been subsequently submitted to preclinical immunogenic evaluation in mice in the presence of QS-21 as an adjuvant. Through standard ELISA assay, this vaccine candidate showed high promise in inducing IgG and IgM antibodies against each of the five individual carbohydrate antigens. In addition, FACS analysis indicated that these antibodies were able to react with MCF-7 breast cancer cell lines expressing these five carbohydrate antigens.
Authors	Jianglong Zhu, Qian Wan, Dongjoo Lee, Guangbin Yang, Maria K Spassova, Ouathek Ouerfelli, Govind Ragupathi, Payal Damani, Philip O Livingston, Samuel J Danishefsky
Journal	Journal of the American Chemical Society (J Am Chem Soc) Vol. 131 Issue 26 Pg. 9298-303 (Jul 08 2009) ISSN: 1520-5126 [Electronic] United States
PMID	19518111 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, Tumor-Associated, Carbohydrate Cancer Vaccines Maleimides Vaccines, Synthetic maleimide Hemocyanins keyhole-limpet hemocyanin
Topics	Animals Antibody Formation (immunology) Antigens, Tumor-Associated, Carbohydrate (chemistry, immunology) Binding Sites, Antibody Breast Neoplasms (immunology, prevention & control) Cancer Vaccines (chemistry, immunology) Cell Line, Tumor Female Hemocyanins (chemistry, immunology) Humans Male Maleimides (chemistry) Mice Mice, Inbred C57BL Prostatic Neoplasms (immunology, prevention & control) Vaccines, Synthetic (chemistry, immunology)

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