RNA containing composition for treatment of tumor diseases

Abstract

The present invention relates to RNA containing compositions for use in the treatment or prophylaxis of tumor and / or cancer diseases, to a pharmaceutical composition, to a kit and to uses of the RNA containing compositions for the treatment or prophylaxis of tumor and / or cancer diseases.

Description

[0001]This application is a continuation of U.S. application Ser. No. 15 / 136,295, filed Apr. 22, 2016, which claims the priority of European Application No. 15001191.4, filed Apr. 22, 2015, the entirety of each of which is incorporated herein by reference.[0002]The sequence listing that is contained in the file named “CRVCP0175USC1.txt”, which is 18,428 KB (as measured in Microsoft Windows) and was created on Feb. 12, 2018, is filed herewith by electronic submission and is incorporated herein by reference.INTRODUCTION[0003]The present invention relates to RNA containing compositions for use in the treatment or prophylaxis of tumor and / or cancer diseases, to a pharmaceutical composition, to a kit and to uses of the RNA containing compositions for the treatment or prophylaxis of tumor and / or cancer diseases.[0004]Cancer, also known as malignant tumor, describes a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. In 2012...

AI Technical Summary

Benefits of technology

[0086]It has been found by the inventors that intratumoral application respectively administration of the RNA containing composition according to the invention is capable of effectively treating tumor and / or cancer diseases and related disorders. It has been shown that intratumoral application is surprisingly effective in decreasing tumor size. Moreover the application of the RNA containing composition according to the invention was able to increase survival in animal models.

[0650]Liposomes are colloidal lipid-based and surfactant-based delivery systems composed of a phospholipid bilayer surrounding an aqueous compartment. They may present as spherical vesicles and can range in size from 20 nm to a few microns. Cationic lipid-based liposomes are able to complex with negatively charged nucleic acids via electrostatic interactions, resulting in complexes that offer biocompatibility, low toxicity, and the possibility of the large-scale production required for in vivo clinical applications. Liposomes can fuse with the plasma membrane for uptake; once inside the cell, the liposomes are processed via the endocytic pathway and the genetic material is then released from the endosome / carrier into the cytoplasm. Liposomes have long been perceived as drug delivery vehicles because of their superior biocompatibility, given that liposomes are basically analogs of biological membranes, and can be prepared from both natural and synthetic phospholipids (Int J Nanomedicine. 2014; 9: 1833-1843).

Problems solved by technology

The use of DNA entails the risk of the DNA being inserted into an intact gene of the host cell's genome by e.g. recombination.

In this case the affected gene may be mutated and inactivated or may give rise to misinformation.

Another risk of using DNA as a pharmaceutical agent is the risk of inducing pathogenic anti-drug antibodies(anti-DNA antibodies) in the patient, which may result in a (possibly fatal) immune response.

This means that the cells of the innate system recognize and respond to pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host.

It usually does not have an open reading frame and thus does not provide a peptide-antigen or immunogen but elicits an innate immune response e.g. by binding to a specific kind of Toll-like-receptor (TLR) or other suitable receptors.

The occurrence of side reactions sets practical limits for the length of synthetic oligonucleotides (up to about 200 nucleotide residues), because the number of errors increases with the length of the oligonucleotide being synthesized.

Decoy receptors: Decoy receptors recognize certain growth factors or cytokines with high affinity and specificity, but are structurally incapable of signaling or presenting the agonist to signaling receptor complexes.

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