A method of treating a patient who has gastric cancer, gastrointestinal cancer, colorectal cancer, pancreatic cancer, lung cancer, and/or renal cancer includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide. A pharmaceutical composition contains activated T cells that selectively recognize cells in a patient that aberrantly express a peptide, and a pharmaceutically acceptable carrier, in which the T cells bind to the peptide in a complex with an MHC class I molecule, and the composition is for treating the patient who has gastric cancer, gastrointestinal cancer, colorectal cancer, pancreatic cancer, lung cancer, and/or renal cancer. A method of treating a patient who has cancer includes administering to said patient a composition comprising a peptide in the form of a pharmaceutically acceptable salt, thereby inducing a T-cell response to the cancer.

Novel immunotherapy against several tumors including gastrointestinal and gastric cancer

Provided are methods of treatment for tumors. In particular, methods are provided for use of a chemically modified IL- 10 to treat tumors.

Use of pegylated il-10 to treat cancer

The invention refers to an oligonucleotide consisting of 10 to 20 nucleotides of selected regions of the TGF-beta1, TGF-beta2 or TGF-beta3 nucleic acid sequence, which comprises modified nucleotides such as LNA, ENA, polyalkylene oxide-, 2'-fluoro, 2'-O- methoxy and/or 2'-O-methyl modified nucleotides. The selected regions are preferably the region of nucleic acid no. 1380 to 1510, no. 1660 to 1680, no. 2390 to 2410, or no. 2740 to 2810 of the TGF-beta2 nucleic acid sequence of SEQ ID NO. 1, specific regions of the TGF-beta1 nucleic acid sequence of SEQ ID NO. 149, or specific regions of the TGF-beta3 nucleic acid sequence of SEQ ID No. 267. The invention further relates to pharmaceutical compositions comprising such oligonucleotide, wherein the composition or the oligonucleotide is used in the prevention and/or treatment of a malignant and/or benign tumor, an immunologic disease, fibrosis, glaucoma, etc..

Modified TGF-beta2 oligonucleotides

Method for producing a modified oligonucleotide, wherein at least one polymer, preferably polyalkylene oxide, and/or a compound is covalently bound to the 5´-end or the 3´-end of the oligonucleotide via native ligation forming a native ligation site, with the proviso that the polymer and/or the compound is not a protein or peptide, if only the 5´-end of the oligonucleotide is modified by binding of the polymer or compound via native ligation. The invention is further directed to a modified oligonucleotide obtainable by the inventive method as well as the use of such modified oligonucleotide for the preparation of a medicament for preventing and/or treating a tumor, formation of metastasis, an immune disease or disorder, a cardiovascular disease or disorder, and/or a viral disease or disorder.

Method for selective oligonucleotide modification

There is provided the use of monomeric TGF-βs, or there fragments or derivatives, as medicaments. These medicaments preferably comprise monomeric TGF-β3, or fragments or derivatives thereof. The medicaments provided may be used in the acceleration of wounding and/or the inhibition of scarring, in the promotion of epithelial regeneration, or in the prevention and/or treatment of fibrotic disorders.

Medicaments and proteins based on tgf-beta monomers for the treatment of wounds

The present invention is related to pharmaceutical compositions for the inhibition of metastases and treatment of cancer such as bladder carcinoma, colon cancer, endometrial cancer, hepatocellular carcinoma, leukemia, lymphoma, melanoma, non-small cell lung cancer (NSCLC), ovarian cancer, pancreatic cancer, prostate cancer, soft tissue cancer, renal cancer, osteosarcoma, mesothelioma, myeloma multiple, bladder carcinoma and esophagcal cancer as well as the use of these pharmaceutical compositions for the treatment of said metastases and cancers. Another aspect of this invention are new antisense oligonucleotides inhibiting the formation of human interleukin 10 and their synthesis. A further aspect of this invention is the use IL-10 antisense oligonucleotides for the preparation of pharmaceutical compositions and for the treatment of cancer and metastases.

Use of an oligonucleotide or its active derivative for the preparation of a pharmaceutical composition for inhibiting the formation of metastases in cancer treatment

Proc Amer Assoc Cancer Res, Volume 45, 2004

2955 

Transforming growth-factor-beta (TGF-beta) plays a pivotal role in malignant progression by inducing key mechanisms including immunosuppression, metastasis, angiogenesis and tumor cell proliferation. With a 5-year-survival rate of less than 1% pancreatic cancer is one of the most aggressive human cancers. Overexpression of TGF-beta2 in malignancies correlates with decreased survival and is associated with advanced tumor stage. In pancreatic cancer patients TGF-beta2 levels were significanty elevated (median: 1198 pg/ml; range: 319-1713 pg/ml) as compared to healthy controls (median: 378 pg/ml; range: 241-575 pg/ml). Aiming at a highly specific anti-tumor therapy, AP 12009, a phosphorothioate antisense oligonucleotide specific for the human TGF-beta2 mRNA, has been developed. AP 12009 has already shown efficacy in phase I/II clinical studies as therapy for high-grade glioma. The overall median survival time was prolonged compared to literature data on temozolomide and significant and persistent tumor responses including one complete tumor remission were documented. Similar to the preclinical data obtained in glioma cells, AP 12009 significantly reduced the TGF-beta2 secretion in several human pancreatic cancer cell lines (Hup-T3, Hup-T4, PA-TU 8902). In functional assays AP 12009 inhibited pancreatic tumor cell proliferation in a dose-dependent manner by up to 76%. Migration of PA-TU 8902 cells was completely blocked as compared to untreated and TGF-beta2 antibody treated controls in a spheroid migration model. Additionally, AP 12009 reversed TGF-beta2 mediated immunosuppression in an allogenic Hup-T3 system targeted by IL-2 activated PBMC (LAK cells) derived from healthy donors. After AP 12009 treatment LAK cell cytotoxicity was increased in a donor-dependent manner up to 800% of the untreated control at effector/target ratios of 1:1.25 to 1:20. Safety pharmacology of AP 12009 was assessed in cynomolgus monkeys. After short-term infusion no observed adverse effect levels (NOAEL) were between 5 - 20 mg/kg b.w. for complement activation, cardiovascular and clotting system, respectively, and below 5 mg/kg b.w. for hematological parameters. Subchronic toxicity studies revealed a NOAEL of 1 mg/kg b.w./day after 4 weeks continuous i.v. infusion in both rats and cynomolgus monkeys. Single intravenous bolus in mice and rats did not cause any toxic symptoms up to 100 mg/kg b.w. (LD50: 706 mg/kg b.w. for mice; 1,175 mg/kg for rats). Based on the preclinical efficacy in tumor proliferation, migration and inhibition of escape from immunosurveillance, the favorable toxicity profile in animal studies, and the successful application of AP 12009 in clinical studies with glioma patients, a multi-site dose-escalation trial with AP 12009 in pancreatic carcinoma is currently in preparation.

TGF-beta2 suppression in pancreatic cancer by the antisense oligonucleotide AP 12009: Preclinical efficacy data

Utilisation d'un oligonucléotide ou d'un dérivé actif pour la préparation d'une composition pharmaceutique inhibant la formation de métastases dans le traitement du cancer

Verwendung eines Oligonukleotide oder seiner aktiven Ableitung für die Zubereitung einer pharmazeutische Zusammensetzung zur Hemmung der Metastasenbildung in Krebsbehandlung

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Use of an oligonucleotide or its active derivative for the preparation of a pharmaceutical composition for inhibiting the formation of metastases in cancer treatment

TGF-beta2 suppression in pancreatic cancer by the antisense oligonucleotide AP 12009: Preclinical efficacy data

Utilisation d'un oligonucléotide ou d'un dérivé actif pour la préparation d'une composition pharmaceutique inhibant la formation de métastases dans le traitement du cancer

Verwendung eines Oligonukleotide oder seiner aktiven Ableitung für die Zubereitung einer pharmazeutische Zusammensetzung zur Hemmung der Metastasenbildung in Krebsbehandlung