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Improved immunotherapy

A technology of therapeutic dose and product, applied in the field of enhancing anti-tumor immune response, can solve problems such as uneven results

Inactive Publication Date: 2005-12-07
ML LAB PLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Overall, however, trials have had mixed results and have not yielded credible improvements in treatment regimens

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0108] Materials and methods

[0109] cell culture

[0110] 4T1, mouse breast cancer cells, was obtained from ATCC (CRL-2539). EJ-6-2-Bam-6a was obtained from ATCC (CRL-1888) and was produced by transfecting NIH / 3T3 with human EJ bladder cancer cell DNA. PER.C6 cells (lit) were obtained from IntroGene (Leiden, Netherlands). 911 cells were provided by Professor L.Young (CRC Cancer Research Institute, University of Birmingham, UK), containing 10% FCS, 10mM MgCl 2 and antibiotics in DMEM medium. 4T1 and EJ-6-2-Bam-6a were cultured in the manner suggested by the provider.

[0111] Plasmid construction

[0112] pTX0374 was constructed by cloning a 1.6 kb BglII-BamHI fragment containing the human CMV promoter linked to the E. coli ntr gene (NTR: E. coli B / r nitroreductase gene amplified from genomic DNA) into pSW107. pRAJ 43BP4 is a pUC19 plasmid containing mouse GM-CSF cDNA, a kind gift from Prof. L. Young (CRC Cancer Research Institute, University of Birmingham, UK). CET902...

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Abstract

The invention provides an improved method of inducing an immune response against targeted cells. Using gene therapy to express both a toxin or prodrug converting enzyme as a means of killing a targeted cell type and also stress response protein (in particular, a heat shock protein) enhances the subsequent immune response directed against such cells. The method is particularly applicable to inducing an immune response against cancer cells. Also provided are polynucleotides, products and vectors for use in such a method.

Description

field of invention [0001] The invention relates to the field of immunotherapy, in particular to enhancing anti-tumor immune response. Background of the invention [0002] One approach to treating tumors is to introduce into tumor cells genes that encode enzymes that convert relatively low-toxicity prodrugs into potent cytotoxic drugs. Systemic administration of this prodrug is tolerated by the body because it is converted to toxic derivatives by prodrug-converting enzymes expressed by cells only in the tumor area. This approach is called gene-directed enzyme prodrug therapy (GDEPT), or virus-directed prodrug therapy (VDEPT) with gene delivery by recombinant viral vectors (McNeish et al., 1997). [0003] Examples of prodrugs and prodrug converting enzymes used in this pathway include ganciclovir and HSV thymidine kinase, 5-fluorocytosine and cytosine deaminase, cyclophosphamide or acetaminophen Phenol and cytochrome P450, and the aziridinyl prodrug CB1954 (5-(aziridin-1-yl)...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/00A61K39/00C07K14/47C12N9/02C12N9/06C12N15/861
CPCC12N9/0028A61K2039/55522C12N15/86A61K39/0011C07K14/47C12N2710/10343C12N9/0036A61K38/00C12N9/0077A61K2039/55516A61P35/00Y02A50/30
Inventor 卡伊·斯特凡·利平斯基哈基姆·德杰哈
Owner ML LAB PLC