10 november 2011: Wie advexin intypt in pubmed krijgt keur aan studies, maar veelal laboratorium of dierstudies. Als u geinteresseerd bent in dit vaccin kunt u wellicht eens in deze selectie zoeken. http://www.ncbi.nlm.nih.gov/pubmed?term=advexin

29 oktober 2004: bron: persbericht van Introgen Therapeutics

Na de volgens Introgen succesvolle trials met Advexin bij vooral hoofd- en halstumoren lijkt nu ook dit vaccin, net als of samen met lichaamseigene dendritische cellen, succesvol te kunnen worden toegepast bij niet-klein-cellige longkanker en borstkanker. Uit proeven bij muizen bleek dat nadat zij met lichaamseigene dendritische cellen of met dit vaccin waren ingespoten en een maand later de muizen werden ingespoten met kankercellen die voor 100% zeker kanker zouden veroorzaken dat in de groep muizen die of met dit vaccin of met dendritische cellen waren ingespoten er slechts 15% kanker ontwikkelden. Opvallend is wel dat er geen onderscheid gemaakt wordt tussen de groep met toegediend de lichaamseigene dendritische cellen en de vaccingroep. Misschien begrijp ik het verkeerd maar volgens mij zijn er toch echt twee groepen gevolgd, maar worden de resultaten uit beide groepen bij elkaar gevoegd. Dat het vaccin dan goed zou werken of dat juist de dendritische cellen voor dit resultaat zorgden is m.i. niet duidelijk uit dit persbericht. Een studieomschrijving ter controle van de gemelde resultaten hebben we nergens kunnen vinden. Wel kunt u hier op deze website van Clinical Oncology Research een zeer uitgebreid, maar wel in medische taal geschreven overzichtsartikel lezen over ontwikkelingen van gentherapie en dan vooral over deze p53 gebaseerde gentherapie. Wie echter klikt op de op genoemde website aanwezige deeplink naar clinical trials ziet dat de resultaten toch wel erg pover zijn tot nu toe. Hieronder eerst de enige studieomschrijving over Advexin die we in Medline kunnen vinden en daarna het persbericht van 20 oktober 2004.

BioDrugs. 2003;17(3):216-22.

INGN 201: Ad-p53, Ad5CMV-p53, Adenoviral p53, INGN 101, p53 gene therapy--Introgen, RPR/INGN 201.

[No authors listed]
Introgen's adenoviral p53 gene therapy [INGN 201, ADVEXIN] is in clinical development for the treatment of various cancers. The p53 tumour suppressor gene is deleted or mutated in many tumour cells and is one of the most frequently mutated genes in human tumours. INGN 201 has been shown to kill cancer cells directly. In August 2002, Introgen announced plans to file an application for INGN 201 with the European Agency for the Evaluation of Medicinal Products (EMEA) for the treatment of head and neck cancer; the European filing will be submitted simultaneously with the previously scheduled (planned for 2004) submission of a Biologics License Application (BLA) for ADVEXIN to the US FDA. On 20 February 2003, INGN 201 received orphan drug designation from the US FDA for head and neck cancer. INGN 201 is available for licensing although Introgen favours retaining partial or full rights to the therapy in the US.Introgen Therapeutics and its collaborative partner for the p53 programme, Aventis Gencell, have been developing p53 gene therapy products. The agreement was originally signed by Rhone-Poulenc Rorer's Gencell division, which became Aventis Gencell after Rhone-Poulenc Rorer merged with Hoechst Marion Roussel to form Aventis Pharma. According to the original agreement, Introgen was responsible for phase I and preclinical development in North America, while Aventis Gencell was responsible for clinical trials conducted in Europe and for clinical trials in North America beyond phase I. In April 2001, Aventis Gencell and Introgen restructured their existing collaboration agreement for p53 gene therapy products. Aventis Gencell indicated that p53 research had suffered from internal competition for resources and was pulling back from its development agreement with Introgen for p53 gene therapy products. Introgen will assume responsibility for worldwide development of all p53 programmes and will obtain exclusive worldwide commercial rights to p53-based gene therapy products. Aventis Gencell will increase its equity stake in Introgen by investing $US 20 million in non-voting preferred shares of Introgen that will be convertible to Introgen common shares at a premium to the market price. Introgen will also receive a 5% equity stake in Aventis Gencell. Introgen intends to use the proceeds of Aventis Gencell's investment to fund the commercialisation of the p53 gene therapy product and to begin building its internal sales and marketing division to support the products anticipated market introduction. In April 2001, Aventis Pharma announced that it intended to spin off its gene therapy division, Aventis Gencell, as a separate operating company. In mid-2002, Aventis Pharma was still attempting to spin off Aventis Gencell but negotiations with venture capital partners had failed. Gene Logic (formerly OncorMed) of the US was contracted by Introgen to perform the p53 status testing for RPR/INGN 201 phase I clinical trials. In February 2003, Introgen announced it will streamline its phase III clinical trials for head and neck cancer to reduce spending, and that INGN 201 received Orphan Drug Status for head and neck cancer in the US. According to results (published in January 2003) of Introgen's phase II study of non-metastatic patients with non-small cell lung cancer (ineligible to receive surgery or combination therapy with radiation and cancer chemotherapy) treated with INGN 201 combined with radiation therapy, approximately 60% of patients' primary tumours regressed or disappeared after the combination therapy, as assessed by both biopsies and by CT scans 3 months after treatment. Investigators commented that further randomised trials are needed to follow-up on these observations. In February 2003, Introgen announced that it will move ahead with the development of registration plans for a non-small cell lung cancer indication for INGN 201, and is now including support for lung cancer registration in partnering discussions. RPR/INGN 201 is undergoing phase I trials for the potential treatment of lung, breast, ovarian, bladder, liver and brain cancers. Introgen and Aventis Pharma had signed a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI). NCI will sponsor clinical trials to evaluate and develop RPR/INGN 201 as a potential anticancer agent for these cancer indications. The trials conducted under a NCI-sponsored IND will evaluate RPR/INGN 201 alone and in combination with other anticancer agents. This agreement was originally signed by Rhone-Poulenc Rorer's Gencell. Introgen has completed three phase I clinical trials with INGN 201 in patients with bronchioalveolar cell lung carcinoma, ovarian cancer and recurrent glioblastomas, respectively. Intratumoural injection of RPR/INGN 201 in patients with recurrent glioblastomas was well tolerated and resulted in expression of the p53 protein. Direct administration of RPR/INGN 201 to the lower airways of patients with bronchioalveolar cell lung carcinoma resulted in symptomatic improvement and improved lung function in some patients. In February 2003, Introgen announced that the US Patent and Trademark Office has issued to The Board of Regents of The University of Texas System, patent No. 6,511,847 entitled "Recombinant p53 Adenovirus Methods and Compositions". Introgen Therapeutics is the exclusive licensee of this patent. The patent covers any adenoviral DNA molecules that encode the p53 gene positioned under the control of a promoter. Such a DNA molecule forms the genetic core of Introgen's ADVEXIN cancer therapy. Introgen's ADVEXIN therapy is now covered by up to ten separate US patents relevant to the product including compositions, therapeutic methods of administering the product in virtually any form, alone and in conjunction with the most widely used chemotherapeutic and radiation treatments, as well as its production. Introgen has a number of US patents that relate to the clinical use of ADVEXIN in cancer as monotherapy or in combination with one or more chemotherapeutic drugs, radiation therapies, or other agents that have a damaging effect on the DNA or survival of (i.e. 2-methoxyestradiol, patent No. 6,410,029) cancer cells. In July 2002, the US Patent and Trademark Office issued to The Board of Regents of The University of Texas System US patent No. 6,410,010. The patent broadly covers all adenoviral p53 compositions (including ADVEXIN), therapeutic and otherwise, that express adequate p53 in amounts sufficient to suppress the growth of or kill cancer cells in patients. The patent also covers adenoviral p53 that incorporates a specific type of promoter that helps cells to express the p53 tumour suppressor gene. Introgen is the exclusive licensee of this composition of matter patent covering ADVEXIN. In December 2002, Aventis Pharmaceuticals was issued US patent No. 6,262,032 B1 entitled "Method of Destroying Hyperproliferative Cells by Combining p53 and Taxoid Treatment". Introgen has an exclusive license to this patent and is using this type of combination therapy in its breast cancer trial. Introgen expects to realise $US 2.5-3 million from sales of INGN 201. En hier het persbericht van 20 oktober 2004:

SEATTLE, Oct. 20 /PRNewswire-FirstCall/ -- Introgen Therapeutics, Inc. (Nasdaq: INGN) today announced preclinical data demonstrating the promise of its INGN 225 therapy as a cancer vaccine. The data were presented yesterday at the Third Annual AACR International Conference on Frontiers in Cancer Prevention Research, being held in Seattle. INGN 225 is a therapeutic consisting of a cancer patient's own immune cells treated with an adenovector carrying the human p53 gene, Ad-p53. INGN 225 is currently in Phase 1/2 trials in patients with small cell lung cancer and breast cancer. Introgen is also developing Ad-p53, or ADVEXIN(R), in phase 3 clinical trials for head and neck cancer, and for a variety of other cancers.
Previous studies have shown that p53 is a critical tumor suppressor gene, whose function is to prevent tumor formation. Mutations in p53 are required for tumor formation. These characteristics make p53 protein an ideal target for a cancer vaccine. In normal cells, p53 is found at very low levels and its expression is very tightly controlled. In cancer cells however, p53 fails to function normally and often accumulates to high levels. This high level of abnormal expression of p53 is used by the immune system to identify and destroy tumor cells following INGN 225 vaccination. "We believe that these studies highlight the great potential of INGN 225 for the treatment of cancer, and we are equally excited by the prospect of using this technology to prevent cancer," said Sunil Chada, Ph.D., Introgen's director of Research and Development. "The ability of INGN 225 to stimulate natural immunity and kill cancer cells is an important advance in the development of cancer vaccines. INGN 225 is a good example of how we can combine molecular therapies with the body's own immune system to develop new cancer vaccine strategies."
The studies presented today were designed to assess the activity of p53-directed immunotherapy and specifically, the ability of p53-treated immune system cells, termed dendritic cells, to generate immunity against cancer cells that over-express p53. Mice were vaccinated with their own dendritic cells or with INGN 225. After 24 days, the mice were injected with a dose of cancer cells that previously has been shown to give rise to cancer in 100 percent of animals tested. In these studies, up to 85 percent of animals were protected from developing tumors. INGN 225 also was assessed for its effect on existing tumors and demonstrated a significant reduction in tumor growth compared with controls. Importantly, activation of the immune system to recognize high levels of p53 expressed in cancer cells did not result in any damage to normal tissue, indicating that this approach should have a very good safety profile. "The ability to activate a patient's immune system is a key advantage of using this type of therapeutic approach," said Dmitry Gabrilovich, M.D., Associate Professor of Oncology at the H. Lee Moffitt Cancer Center and principal investigator of the INGN 225 lung cancer clinical trial. "In these studies, combining the power of Ad-p53 with dendritic cell technology enabled us to generate potent immune responses and prevent tumor growth in animal models. These data validate the use of tumor suppressor antigens as therapeutic targets, and demonstrate that adenovectors provide an efficient method of stimulating dendritic cells so that they can generate a powerful anti-cancer immune response. We hope to ultimately be able to expand our ongoing therapeutic studies in patients into future prevention of this terrible disease."

Introgen is a leading developer of biopharmaceutical products designed to induce therapeutic protein expression using non-integrating gene agents for the treatment of cancer and other diseases. Introgen maintains integrated research, development, manufacturing, clinical and regulatory departments and operates a commercial-scale, CGMP manufacturing facility. Certain statements in this press release that are not strictly historical may be "forward-looking" statements, which are based on current expectations and entail various risks and uncertainties. Such forward-looking statements include, but are not limited to, those relating to Introgen's future success with its clinical development program for INGN 225 in the treatment of breast and lung cancers. There can be no assurance that Introgen will be able to commercially develop gene-based drugs, that necessary regulatory approvals will be obtained or that any clinical trials or studies undertaken will be successful or that the proposed treatments will prove to be safe and/or effective. The actual results may differ from those described in this press release due to risks and uncertainties that exist in Introgen's operations and business environment, including, but without limitation, Introgen's stage of product development and the limited experience in the development of gene- based drugs in general, Introgen's dependence upon proprietary technology and current competition, history of operating losses and accumulated deficits, reliance on collaborative relationships, and uncertainties related to clinical trials, the safety and efficacy of Introgen's product candidates, the ability to obtain the appropriate regulatory approvals, patent protection and market acceptance, as well as other risks detailed from time to time in Introgen's filings with the Securities and Exchange Commission. Introgen undertakes no obligation to publicly release the results of any revisions to any forward- looking statements that reflect events or circumstances arising after the date hereof.

Editor's Note: For more information on Introgen Therapeutics, or for a menu of archived press releases, please visit Introgen's Website at: Introgen.

Contact:
Introgen Therapeutics, Inc.
C. Channing Burke
(512) 708 9310 Ext. 322


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