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Mucin peptide with immunoenhancing properties

a peptide and immunoenhancing technology, applied in the field of peptides with immunoenhancing properties, can solve problems such as biocompatibility with formulations

Inactive Publication Date: 2005-05-05
UNIV OF MIAMI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018] It is one object of the invention to provide an isolated peptide, polypeptide or protein comprising the amino acid sequence VSIGLSFPMLP (SEQ ID NO: 1), or an analog or derivative thereof. The peptide of the invention has immunoenhancing properties and can be used in pharmaceutical compositions and vaccines.
[0021] It is another object of the invention to provide a nucleic acid encoding the peptide, polypeptide or protein of the invention, or derivative or analog thereof. The nucleic acids of the invention may be produced recombinantly, synthetically, or by any means available to those of skill in the art, and may be cloned using techniques known in the art. In this regard, the invention also includes a vector comprising the nucleic acid of the invention, and a host cell comprising the nucleic acid of the invention.
[0028] It is also an object of the invention to provide a method of preventing or treating a disease or disorder by the administration of a safe and effective dose of a vaccine or pharmaceutical composition of the invention. Safe and effective dosages of the pharmaceutical compositions and vaccines of the invention can be determined by persons of skill in the art without undue experimentation. A safe and effective dosage is considered to be one that can be administered to a subject to produce a beneficial effect on the subject's immune response without causing adverse, effects that would be considered unacceptable by persons of skill in the art. It will be appreciated that any such adverse effects must be balanced against the benefits of the treatment of the invention, alternative available treatments, and other factors familiar to those of skill in the art. In a preferred embodiment, the invention provides a method for the prevention or treatment of tumors, particularly cancerous tumors.

Problems solved by technology

It can be produced under conditions that satisfy standards for biologicals intended for medical or veterinary treatment, and is biocompatible with formulations used for therapy and prophylaxis.

Method used

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  • Mucin peptide with immunoenhancing properties
  • Mucin peptide with immunoenhancing properties
  • Mucin peptide with immunoenhancing properties

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0056] DA-3 mammary tumor cells were transfected as described in Materials and Methods with either the transmembrane and secretory isoforms of the human MUC1. The success of the transfections was proven by staining the cells for the presence of the MUC1 tandem repeat using the H23 antibody specific for this sequence (5). The resulting cell lines were used in in vivo experiments to determine the incidence and time of tumor appearance in BALB / c mice. As seen in Table 1, implantation of DA-3, DA-3 / neo and DA-3 / TM mammary tumor cells into mice gave rise to palpable tumors of approximately the same size by seven days and by 15 days essentially all animals had sizable tumors.

TABLE 1Incidence and Time of Tumor Appearance in BALB / c MiceTumorDay of Tumor appearanceType715253712+ monthsDA-332 / 3838 / 38DA-3 / neo17 / 2524 / 2525 / 25DA-3 / TM29 / 3633 / 3635 / 3636 / 36DA-3 / sec 0 / 70 0 / 70 1 / 70 1 / 701 / 70

Surprisingly, the DA-3 cells transfected with the MUC1 secreted form (DA-3 / sec) failed to cause tumor developme...

example 2

[0057] A trivial explanation to these results could be that the transfection process had selectively impaired the basic growth potential of the DA-3 / sec cells. To test this possibility we investigated the in vitro growth characteristics of the four types of DA-3 tumor cells. As shown in FIG. 2, the parent cell line and all the various transfectants grew with similar kinetics in vitro. In fact, the DA-3 / sec cells seemed to proliferate better than the other cell lines, indicating that the in vitro growth potential of these cells has not been altered by the transfection manipulations.

example 3

[0058] In order to determine whether the DA-3 / sec cells had lost all tumorigenic potential in vivo, all four DA-3 cell lines were implanted in nu+ / nu+BALB / c mice and the incidence of tumor appearance and tumor size at various times were assessed. FIG. 3 shows that the DA-3, DA-3 / neo, and DA-3 / TM cells cause palpable tumors by seven days after implantation in BALB / c nude mice and they grew in a manner similar to that of intact BALB / c animals. In contrast with the results in Table 1 and FIG. 1, DA-3 / sec tumor cells gave rise to tumors in 30% of all nude mice by 14 days and by 25 days all these animals had tumors. Thus, the lack of tumor growth in the intact BALB / c mice implanted with the DA-3 / sec cells appears to be immunologically controlled, since implantation of this tumor in nude mice resulted in 100% tumor takes, albeit at a slower time of appearance. These results were repeated using other two DA-3 tumor cells separately transfected with the expression plasmid harboring the secr...

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Abstract

An isolated peptide or polypeptide containing the sequence VSIGLSFPMLP (SEQ ID NO:1), found in the secreted form of human MUC1, that enhances an immune response when administered to a mammal, compositions containing the peptide, host cells producing the peptide and methods of use. The peptide or polypeptide may be conjugated to a carrier protein and administered as part of a vaccine or immunogenic composition for prevention or treatment of a disease or disorder.

Description

[0001] This application claims the priority of U.S. provisional application No. 60 / 280,137, filed Apr. 2, 2001, which is incorporated herein in its entirety.BACKGROUND OF THE INVENTION [0002] 1. Field of the Invention [0003] The invention relates to a mucin peptide with immunoenhancing properties, pharmaceutical compositions containing the peptide, and methods of treating or preventing cancer. [0004] 2. Background Information [0005] The MUC1 gene is expressed in normal epithelium and several types of human cancers and at very high levels in breast tumors (1). A major product of this gene is a polymorphic type 1 transmembrane molecule consisting of a large, heavily glycosylated extracellular domain, a transmembrane domain, and a 72 amino acid cytoplasmic tail (2). The polymorphism mainly derives from variations in the numbers of a 20 amino acid tandem repeat unit present in the extracellular domain. A secreted MUC1 isoform (MUC1 / sec) (3) has also been found, that includes a sequence ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K48/00A61K38/00A61K39/00A61K39/39A61P35/00A61P37/02A61P37/04C07K7/06C07K7/08C07K14/47C12N5/10C12N15/09
CPCA61K39/0011C07K14/4727A61K2039/55516A61K39/39A61P35/00A61P37/02A61P37/04A61K39/00117A61K38/16
Inventor LOPEZ, DIANAHERBERT, LYNNDORSEY, MANTLEYKRAUS, GUNTERHNATYSZYN, H.
Owner UNIV OF MIAMI
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