Therapeutic compositions and methods of use for treating cancer

a technology of compositions and cancer, applied in the field of compositions and methods for treating cancer, can solve the problems of affecting the effectiveness unable to detect visually, regression, and/or destruction of micrometastases, etc., and impedes the effect of circulating anti-tumor immune respons

Inactive Publication Date: 2018-04-19
AGALIMMUNE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Tumors may develop in cancer patients because the immune system fails to detect tumor cells as cells that ought to be destroyed.
Such an immune response will destroy any untreated lesions (for example, those that cannot be accessed for treatment nor removed by surgery) and results in immune mediated detection, regression, and / or destruction of micrometastases which cannot be detected visually and are not detectable by imaging.
Often, the size of a tumor impedes the efficacy of a circulating anti-tumor immune response in a timely manner.
The problem with this approach is that GM-CSF is used to recruit antigen-presenting cells to the lesion site, but uptake of tumor material by these cells thereafter is random.
Antigen-presenting cells are quite effective in taking up small particulate material and soluble antigens but are inefficient at internalizing cells or larger cell fragments.

Method used

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  • Therapeutic compositions and methods of use for treating cancer
  • Therapeutic compositions and methods of use for treating cancer
  • Therapeutic compositions and methods of use for treating cancer

Examples

Experimental program
Comparison scheme
Effect test

example 1

on of Preliminary Studies for Expression of Alpha-Gal Epitopes on Tumor Cells by Transduction with an Adenovirus Vector Containing the α1,3GT Gene

[0145]Induction of expression of alpha-gal epitopes (Gal-alpha1-3Gal-beta1-4GlcNAc-R) on human tumor cells was previously studied by transduction with replication defective adenovirus vector that contains the α1,3GT gene as detailed in Deriy et al. Glycobiology 2002, 12: 135-144. For this purpose, the open reading frame (ORF) of the mouse alpha 1,3GT cDNA was inserted into a replication defective adenovirus vector, in which the early genes E1 and E3 genes were deleted. This was achieved by the use of the pAd shuttle plasmid containing the alpha 1,3GT cDNA that allows for homologous recombination of the cDNA into the replication defective adenovirus vector. In this plasmid, the α1,3GT gene was inserted downstream of the cytomegalovirus (CMV) promoter which is a very effective promoter in mammalian cells. The generated adenovirus vector cont...

example 2

n of Alpha-Gal Epitopes on B16-BL6 Melanoma Cells Transduced with Adenovirus Vector Containing the Alpha 1,3-Galactosyltransferase Gene

[0149]In order to achieve introduction of the alpha 1,3-galactosyltransferase gene into cells, this gene was inserted into a replication incompetent adenovirus vector as previously described (Deriy et al. Glycobiology 2002, 12: 135). The resulting vector is designated AdαGT and is very effective in inducing expression of alpha-gal epitopes on human tumor cells (Deriy L et al, supra). The expression of alpha-gal epitopes was determined on AdαGT transduced B16-BL6 melanoma cells. These cells are a subclone of B16 melanoma and are referred to as BL6 cells. The transduction of BL6 cells with AdαGT results in intracellular production of alpha1,3-galactosyltransferase that is encoded by the alpha 1,3-galactosyltransferase gene within the transducing AdαGT. The de novo expression of alpha-gal epitopes on cell surface glycoconjugates following synthesis of t...

example 8

n and Efficacy of a Replication Competent Oncolytic Adenovirus that Encodes a Functional Alpha 1,3-Galactosyltransferase Gene

[0159]The present study describes the production of an Ad5 / 3-Δ24-αGT CRAd (CRAd-αGT), in which the E3 gene was replaced with the murine alpha 1,3-galactosyltransferase (α1,3GT) gene. α1,3GT synthesizes the carbohydrate antigen galactose-alpha-1,3-galactosyl-beta-1,4-N-acetyl-glucosamine-R (alpha-gal). When the virus replicates, the α1,3GT protein is produced along with the viral proteins, the αGT protein subsequently catalyzes the production of alpha-gal. Cell surface alpha-gal is complexed by anti-Gal antibodies, promoting immune activation and uptake of the immune complexes by antigen presenting cells.

[0160]Materials and Methods

[0161]Cell Lines

[0162]A549 (human lung carcinoma) and A375 (human melanoma) cell lines were purchased from the European Collection of Authenticated Cell Cultures (ECCAC). A549 cells were maintained in F-12K+10% fetal bovine serum (FBS...

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Abstract

The present invention relates to compositions and methods for treating cancer. More specifically, the present invention relates to compositions of engineered oncolytic viruses for administration to a subject with cancer that specifically lyse tumor cells and actively target tumor cells and cell debris to antigen presenting cells, in order to generate anti-tumor immunity.

Description

FIELD OF THE INVENTION[0001]The present invention relates to compositions and methods for treating cancer. More specifically, the present invention relates to compositions of engineered oncolytic viruses for administration to a subject with cancer that specifically lyse tumor cells and actively target tumor cells and cell debris to antigen presenting cells, in order to generate anti-tumor immunity.BACKGROUND OF THE INVENTION[0002]Tumors may develop in cancer patients because the immune system fails to detect tumor cells as cells that ought to be destroyed. Tumor cells express autologous tumor antigens in a large proportion of cancer patients. These autologous tumor antigens, also called “neoantigens”, may elicit a protective anti-tumor immune response. Tumor cells, or tumor cell membranes, have to be internalized by antigen presenting cells in order to induce the development of an anti-tumor immune response. However, the immune system in many cancer patients displays an “ignorance” ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K35/761C12N7/00A61K9/00A61P35/00A61P35/02A61K38/45
CPCA61K35/761C12N7/00A61K9/0019A61K9/0053A61K9/0034A61K9/0043A61K9/0031A61P35/00A61P35/02C12Y204/01087A61K38/45C12N2710/10343C12N2710/10371C12N2710/16643C12N2710/16671A61K35/768C12N9/1051C12N2710/10332C12N2710/16632C12N9/10C12Y204/01057
Inventor GALILI, URISHAW, STEVENWESTBY, MICHAEL
Owner AGALIMMUNE
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