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Composition for treating lung cancer, particularly of non-small lung cancers (NSCLC)

a technology for lung cancer and composition, applied in the field of active composition, can solve the problems of uncontrollable difficult to rule out the risk of uncontrolled propagation of introduced genes and viral genes, and poor approach to nsclc, etc., and achieve the effect of stimulating the immune system

Inactive Publication Date: 2016-11-03
CUREVAC AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is about an active (immunostimulatory) composition that can effectively stimulate the immune system to treat lung cancer, especially non-small cell lung cancer (NSCLC). The composition contains at least two antigens, which are preferably different but may also be the same. The antigens can be encoded by one or more RNA molecules. The invention is based on the discovery that a combination of these antigens can effectively stimulate the immune system to treat lung cancer. The composition can also contain other components such as at least one RNA encoding hTERT, which is a human telomerase reverse transcriptase. The invention provides a method for immunostimulation against lung cancer by using an active composition containing specific antigens.

Problems solved by technology

Therapeutic approaches in advanced disease involve—following surgery—both adjuvant chemotherapy and / or adjuvant radiotherapy, whereas chemotherapy as monotherapy (first-line therapy) seems to be an approach associated with relatively poor results.
Even though doubtless there is some improvement in the current therapeutic approaches treatment of lung cancer, especially of NSCLC, is still an uphill-struggle with—given the high mortality rates—a strong need for further, alternative or improved ways of treatment.
Despite these precautions, however, it is not possible to rule out the risk of uncontrolled propagation of the introduced gene and viral genes, for example due to potential recombination events.
This also entails the risk of the DNA being inserted into an intact gene of the host cell's genome by e.g. recombination, with the consequence that this gene may be mutated and thus completely or partially inactivated or may give rise to misinformation.
One particular risk occurs if the DNA is integrated into a gene which is involved in the regulation of cell growth.
In this case, the host cell may become degenerate and lead to cancer or tumor formation.
The integration of such promoters into the genome of the treated cell may result in unwanted alterations of the regulation of gene expression in the cell.
Another risk of using DNA as an agent to induce an immune response (e.g. as a vaccine) is the induction of pathogenic anti-DNA antibodies in the patient into whom the foreign DNA has been introduced, so bringing about a (possibly fatal) immune response.

Method used

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  • Composition for treating lung cancer, particularly of non-small lung cancers (NSCLC)
  • Composition for treating lung cancer, particularly of non-small lung cancers (NSCLC)
  • Composition for treating lung cancer, particularly of non-small lung cancers (NSCLC)

Examples

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Embodiment Construction

[0602]The following examples are intended to illustrate the invention further. They are not intended to limit the subject matter of the invention thereto.

1. Preparation of Encoding Plasmids:

[0603]In the following experiment DNA sequences, corresponding to the respective mRNA sequences end encoding the antigens[0604]hTERT,[0605]WT1,[0606]MAGE-A2,[0607]5T4,[0608]MAGE-A3,[0609]MUC1,[0610]Her-2 / neu,[0611]NY-ESO-1,[0612]CEA,[0613]Survivin,[0614]MAGE-C1, or[0615]MAGE-C2.

[0616]respectively, were prepared and used for in vitro transcription and transfection experiments. Thereby, the DNA sequence corresponding to the native antigen encoding mRNA was increased in GC-content and codon-optimized. Then, the coding sequence was transferred into an RNActive construct (CureVac GmbH, Tübingen, Germany), which has been modified with a poly-A-tag and a poly-C-tag (A70-C30).

2. In Vitro Transcription:

[0617]Based on the recombinant plasmid DNA obtained in Example 1 the RNA sequences were prepared by in v...

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Abstract

The present invention relates to an active (immunostimulatory) composition comprising at least one RNA, preferably a mRNA, encoding at least two (preferably different) antigens capable of eliciting an (adaptive) immune response in a mammal. The invention furthermore relates to a vaccine comprising said active (immunostimulatory) composition, and to the use of said active (immunostimulatory) composition (for the preparation of a vaccine) and / or of the vaccine for eliciting an (adaptive) immune response for the treatment of lung cancer, particularly of non-small cell lung cancers (NSCLC), preferably selected from the three main sub-types squamous cell lung carcinoma, adenocarcinoma and large cell lung carcinoma, or of disorders related thereto. Finally, the invention relates to kits, particularly to kits of parts, containing the active (immunostimulatory) composition and / or the vaccine.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. application Ser. No. 13 / 750,664, filed Jan. 25, 2013, which is a continuation of U.S. application Ser. No. 12 / 682,213, filed Jul. 9, 2010, now abandoned, which is a national phase application under 35 U.S.C. §371 of International Application No. PCT / EP2008 / 008503, filed Oct. 8, 2008, which claims priority to International Application No. PCT / EP2007 / 008770, filed Oct. 9, 2007, the disclosures of which are incorporated herein by reference in their entirety.SEQUENCE LISTING[0002]The sequence listing that is contained in the file named “CRVCP0068USC2.txt”, which is 76 KB (as measured in Microsoft Windows®) and was created on May 3, 2016, is filed herewith via EFS-Web and is hereby incorporated by reference in its entirety.BACKGROUND OF THE INVENTION[0003]The present invention relates to an active (immunostimulatory) composition comprising at least one RNA, preferably a mRNA, encoding at least two (pr...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00
CPCA61K39/0011A61K2039/53A61K2039/575A61K2039/572A61K2039/70A61P11/00A61P35/00A61P37/04A61P43/00A61K2039/86A61K2039/57
Inventor BARNER, MARIJKEPROBST, JOCHENLANDER, THOMASHOERR, INGMAR
Owner CUREVAC AG
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