Glycopeptide and uses thereof

Inactive Publication Date: 2012-02-16
UNIV OF GEORGIA RES FOUND INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0020]Optionally, the pharmaceutical composition contains a liposome. Formulations with liposomes, micelles, or other lipid vesicles may facilitate delivery of the

Problems solved by technology

Numerous studies have shown that this abnormal glycosylation can promote metastasis and hence it is strongly correlated with poor survival rates of cancer patients.
Carbohydrates alone, however, cannot activate helper T-cells and therefore are characterized by poor immunogenicity.
It has proven difficult to overcome the immunotolerance that characterizes these antigens.
However, conjugation of carbohydrates to a carrier protein poses several new problems.
T

Method used

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  • Glycopeptide and uses thereof
  • Glycopeptide and uses thereof
  • Glycopeptide and uses thereof

Examples

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examples

[0158]The present invention is illustrated by the following examples. It is to be understood that the particular examples, materials, amounts, and procedures are to be interpreted broadly in accordance with the scope and spirit of the invention as set forth herein.

example i

Towards a Fully Synthetic Carbohydrate-Based Anti-Cancer Vaccine: Synthesis and Immunological Evaluation of a Lipidated Glycopeptide Containing the Tumor-Associated Tn-Antigen

[0159]In this Example, a fully synthetic candidate cancer vaccine, composed of a tumor associated Tn-antigen, a peptide T-epitope and the lipopeptide Pam3Cys was prepared by a combination of polymer-supported and solution phase chemistry. Incorporation of the glycolipopeptide into liposomes gave a formulation that was able to elicit a T-cell dependent antibody response in mice.

[0160]A common feature of oncogenic transformed cells is the over-expression of oligosaccharides, such as Globo-H, LewisY, and Tn antigens (Lloyd, Am. J Clin. Pathol. 1987, 87, 129; Feizi et al., Trends in Biochem. Sci. 1985, 10, 24-29; Springer, J. Mol. Med. 1997, 75, 594-602; Hakomori, Acta Anat. 1998, 161, 79-90). Numerous studies have shown that this abnormal glycosylation can promote metastasis (Sanders et al., Mol. Pathol. 1999, 52,...

example ii

Non-Covalently Linked Diepitope Liposome Preparations

[0180]In a first set of experiments, the tumor-related carbohydrate B-epitope and the universal T-epitope peptide were incorporated separately into preformed liposomes to form a diepitopic construct. Additionally, the lipopeptide Pam3Cys was incorporated into the liposome with the expectation that it would function as a built-in adjuvant, and thus circumvent the necessity of using an additional external adjuvant, such as QS-21.

[0181]The liposomes were prepared from lipid anchors carrying two different thiol-reactive functionalities, maleimide and bromoacetyl, at their surface. The Pam3Cys adjuvant was also incorporated into the preformed liposome and included a maleimide functionality. Conveniently, the maleimide and the bromoacetyl group show a marked difference in their reactivity towards sulfhydryl groups. The maleimide reacts rapidly with a sulfhydryl compound at pH 6.5, whereas the bromoacetyl requires slightly higher pH 8-9 ...

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Abstract

A glycolipopeptide comprising a carbohydrate component, a peptide component and a lipid component, for use as a therapeutic or prophylactic vaccine. Also provided are monoclonal and polyclonal antibodies that recognize the glycolipopeptide of the invention, as well as uses thereof.

Description

[0001]This application claims the benefit of U.S. Provisional Application Ser. No. 61 / 197,386, filed Oct. 27, 2008, and is continuation-in-part of U.S. application Ser. No. 12 / 217,376, filed on Jul. 3, 2008, which claims the benefit of U.S. Provisional Application Ser. No. 61 / 127,710, filed May 15, 2008, and is also a continuation-in-part of International Application PCT / US2007 / 000158, with an international filing date of Jan. 3, 2007, which in turn claims the benefit of U.S. Provisional Application Ser. Nos. 60 / 755,881, filed Jan. 3, 2006; 60 / 796,769, filed May 2, 2006; and 60 / 809,272, filed May 30, 2006; each of which is incorporated herein by reference in its entirety.STATEMENT OF GOVERNMENT RIGHTS[0002]This invention was made with government support under a grant from the National Cancer Institute of the National Institute of Health (Grant No RO1 CA88986). The U.S. Government has certain rights in this invention.BACKGROUND[0003]A large number of tumor-associated carbohydrate ant...

Claims

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Application Information

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IPC IPC(8): A61K39/00A61K39/395A61K9/127A61K39/12A61K39/02A61K39/42A61K39/40A61K39/002C07K16/00C07K17/00A61P35/00A61P31/12A61P33/02A61P31/04A61P31/14A61P31/18C12N5/16G01N33/53C07K17/02
CPCA61K38/00C12N2740/16134A61K9/127A61K39/385A61K47/4833C12N2770/24211G01N2800/2821C07K16/3076C07K14/4727C07K14/22C07K9/00A61K2039/6075A61K2039/6018A61K2039/57A61K2039/55555A61K2039/55511A61K39/0011A61K39/0008G01N2800/042G01N2400/02C12N2740/16011A61K2039/545C07K16/44A61K47/646A61P31/04A61P31/12A61P31/14A61P31/18A61P33/02A61P35/00A61K39/00117C07K2317/34G01N33/92
Inventor BOONS, GEERT-JANBUSKAS, THERESEHARVEY, ALEX J.INGALE, SAMPATWOLFERT, MARGARETHAWELLS, ROBERT LANCE
Owner UNIV OF GEORGIA RES FOUND INC
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