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Anti-neovasculature preparations for cancer

a technology of ovasculature and preparation, which is applied in the direction of antibody medical ingredients, peptide/protein ingredients, angiogenin, etc., can solve the problems that the treatment of cancer remains challenging, and achieve the effect of rapid tumor appearan

Inactive Publication Date: 2005-11-24
MANNKIND CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0013] Other embodiments relate to methods of evaluating cell-mediated immunity, including immunity directed against a neovasculature antigen. The methods can include the steps of implanting or injecting MHC-transgenic tumor cells into an MHC-transgenic mammal; establishing an immune response in the mammal; and assaying a characteristic to determine cell-mediated immunity in the mammal. The MHC-transgenic mammal can be an HLA-transgenic mammal, such as, for example an HLA-A2 transgenic mammal. In preferred embodiments the mammal can be a mouse. The cell-mediated immunity can be established by vaccination, which in preferred embodiments can take place prior to, concurrent with, or subsequent to transfer of the tumor cells, for example. In preferred embodiments the cell-mediated immunity can be mediated by cytotoxic T lymphocytes. The neovasculature antigen can be preferentially expressed by tumor-associated neovasculature

Problems solved by technology

The treatment of cancer has remained challenging despite the advances in biomedicine.

Method used

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  • Anti-neovasculature preparations for cancer

Examples

Experimental program
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example 1

[0056] A preclinical study was carried out using the already identified antigens PSMA and ED-B disclosed herein. The results of the study revealed excellent candidate epitopes. See table 9 below.

example 1.1

Cluster Analysis (PSMA163-192)

[0057] A peptide, AFSPQGMPEGDLVYVNYARTEDFFKLERDM, PSMA163-192, (SEQ ID NO. 3), containing an A1 epitope cluster from prostate specific membrane antigen, PSMA168-190 (SEQ ID NO. 4) was synthesized using standard solid-phase F-moc chemistry on a 433A ABI Peptide synthesizer. After side chain deprotection and cleavage from the resin, peptide first dissolved in formic acid and then diluted into 30% Acetic acid, was run on a reverse-phase preparative HPLC C4 column at following conditions: linear AB gradient (5% B / min) at a flow rate of 4 ml / min, where eluent A is 0.1% aqueous TFA and eluent B is 0.1% TFA in acetonitrile. A fraction at time 16.642 min containing the expected peptide, as judged by mass spectrometry, was pooled and lyophilized. The peptide was then subjected to proteasome digestion and mass spectrum analysis essentially as described above. Prominent peaks from the mass spectra are summarized in Table 1.

TABLE 1PSMA163-192 Mass Peak Identifi...

example 1.2

Cluster Analysis (PSMA281-310).

[0082] Another peptide, RGIAEAVGLPSIPVHPIGYYDAQKLLEKMG, PSMA281-310, (SEQ ID NO. 18), containing an A1 epitope cluster from prostate specific membrane antigen, PSMA283-307 (SEQ ID NO. 19), was synthesized using standard solid-phase F-moc chemistry on a 433A ABI Peptide synthesizer. After side chain deprotection and cleavage from the resin, peptide in ddH2O was run on a reverse-phase preparative HPLC C18 column at following conditions: linear AB gradient (5% B / min) at a flow rate of 4 ml / min, where eluent A is 0.1% aqueous TFA and eluent B is 0.1% TFA in acetonitrile. A fraction at time 17.061 min containing the expected peptide as judged by mass spectrometry, was pooled and lyophilized. The peptide was then subjected to proteasome digestion and mass spectrum analysis essentially as described above. Prominent peaks from the mass spectra are summarized in Table 3.

TABLE 3PSMA281-310 Mass Peak Identification.CALCU-SEQLATEDIDMASSNO.PEPTIDESEQUENCE(MH+)1...

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Abstract

Disclosed herein are immunogenic compositions, methods of designing immunogenic compositions, methods of treatment using immunogenic compositions, methods of evaluating cell-mediated immunity resulting from immunogenic compositions, research models, and methods of making research models, all of which relate to targeting tumor vasculature.

Description

CROSS REFERENCE [0001] This application is a continuation of U.S. application Ser. No. 10 / 094,699, filed Mar. 7, 2002, entitled “ANTI-NEOVASCULATURE PREPARATIONS FOR CANCER,” which claims priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application Ser. No. 60 / 274,063, filed on Mar. 7, 2001, entitled “ANTI-NEOVASCULATURE PREPARATIONS FOR CANCER,” each of which is hereby incorporated by reference in its entirety.BACKGROUND OF THE INVENTION [0002] Description of the Related Art [0003] The treatment of cancer has remained challenging despite the advances in biomedicine. In recent years two approaches have been described showing much promise: therapeutic vaccines and anti-angiogenesis. [0004] Therapeutic vaccines rely on the observation that cancerous tissues generally express certain antigens preferentially, collectively tumor-associated antigens (TuAA). TuAA include proteins normally expressed selectively by the tissue from which the cancer derives (differentiation antigen...

Claims

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Application Information

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IPC IPC(8): A01K67/027A61K38/00A61K39/00A61K39/395A61P35/00C07K14/515C07K14/74C12N5/02C12N5/06C12N5/08C12P21/08C12Q1/02G01N33/48
CPCA01K67/0271A01K67/0276A61K39/0011C07K14/70539A61K39/39558A61K2039/57A61K39/3955A61P35/00A61P35/04A61K39/001109
Inventor SIMARD, JOHNDIAMOND, DAVID
Owner MANNKIND CORP
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