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Listeria-based EphA2 vaccines

A Listeria, immune response technology, applied in the control or prevention of proliferative cell disease, therapeutic field, able to solve problems such as stenosis

Inactive Publication Date: 2007-01-10
MEDIMMUNE LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] 2.2. Hyperproliferative diseases
[0033] 2.2.5.4. Restenosis
However, unlike other receptor tyrosine kinases, EphA2 retains enzymatic activity in the absence of ligand binding or phosphorylated tyrosine (Zantek et al., 1999, supra)

Method used

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  • Listeria-based EphA2 vaccines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0483] 6.1. Example 1: The life cycle of Listeria

[0484] Figures 1A-1B The life cycle of Listeria monocytogenes, including the steps of endocytosis, phagolysosome lysis, and cell-to-cell spread, is shown in .

Embodiment 2

[0485] 6.2. Example 2: Construction of expressing EphA2 and control Listeria strains

[0486] 6.2.1. Background

[0487] According to the mechanism of heterologous antigen presentation by Listeria through the MHC class I pathway, the expression of heterologous genes and the efficiency of newly synthesized proteins secreted from bacteria into the cytoplasm of infected (antigen-presenting) cells are closely related to CD8+ T cells. is directly related to the intensity of priming and / or activation. Since the level of Ag-specific T cell priming is directly related to the efficacy of the vaccine, the efficiency of heterologous protein expression and secretion is directly related to the strength of the vaccine. Therefore, the efficiency of EphA2 expression and secretion is optimized to maximize the effectiveness of Listeria-based vaccines in terms of initiating and / or activating CD8+ T cell responses specific to the encoded EphA2 protein.

[0488] 6.2.2. Preparation of mutant List...

Embodiment 3

[0591] 6.3. Example 3: Generation of mouse tumor cell lines expressing human EphA2

[0592] 6.3.1. Background

[0593] A mouse immunotherapy model was established for testing the Listeria-based vaccines of the present invention. Three mouse tumor cell lines, CT26 mouse colon carcinoma cell line, B16F10 mouse melanoma cell line and RenCa mouse renal cell carcinoma cell line, were established to express high levels of huEphA2 protein. FACS cell sorting analysis was performed to identify CT26, B16F10 and RenCa tumor cells expressing high levels of huEphA2, pooled and analyzed by Western blot analysis. Clones were further pooled by FACS cell sorting to generate subclones expressing high levels of huEphA2.

[0594] 6.3.2. Selection of CT26 mouse colon cancer cells expressing huEphA2 at a high level

[0595] 6.3.2.1. Lipofectamines TM Transfection analysis of

[0596] Use standard transfection techniques with commercially available Lipofectamine TM , CT26 cells were transfecte...

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Abstract

The present invention relates to methods and compositions designed to treat, control or prevent cancer, particularly metastatic cancer and cancer of T cell origin, and hyperproliferative diseases associated with EphA2 expressing cells. The methods of the invention comprise the use of a Listeria-based EphA2 vaccine. The invention also provides pharmaceutical compositions comprising one or more Listeria-based vaccines of the invention, alone or in combination with one or more other agents useful in the treatment of cancer, in certain embodiments of the invention. In some aspects, the method comprises eliciting CD4 against EphA2 and / or EphA2 expressing cells + and CD8 + T cell response.

Description

[0001] This application claims priority to the following applications: U.S. Provisional Application Serial No. 60 / 511,919 filed October 15, 2003, U.S. Provisional Application Serial No. 60 / 511,719 filed October 15, 2003, filed December 24, 2003 U.S. Provisional Application Serial No. 60 / 532,666 filed March 26, 2004, U.S. Provisional Application Serial No. 60 / 556,631 filed October 2004 (Attorney Docket No. 10271-144-888), and 2004 US Provisional Application (Attorney Docket No. 10271-146-888), filed October 7, each of which is hereby incorporated by reference in its entirety. 1. Technical field [0002] The present invention relates to methods and compositions for treating, controlling or preventing proliferative cell diseases. The invention further relates to Listeria-based compositions that elicit an immune response against hyperproliferative cells and methods of using the compositions. Among other things, the present invention includes vaccines containing Listeria expressin...

Claims

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Application Information

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IPC IPC(8): A61K39/102C12N1/20C07K1/10
Inventor 迈克尔·S·金奇彼得·A·基内尔伊利莎白·布洛克海默小汤姆斯·W·杜宾斯基大卫·N·库克
Owner MEDIMMUNE LTD
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