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The present invention further provides elimination of immune privilege animal cells or tissues, such as tumor cells, and the application of microorganisms by administering at least two microorganisms and purposes, wherein said microorganism is simultaneously, sequentially or given intervals, wherein described microorganisms accumulate in cells of immune privilege, so that the animal against the immune cells or tissue autoimmune exemption. b balanced release pathogenicity between the tumor antigen. As used herein, can be converted to bioluminescence substrate means susceptible to chemical reactions such as oxidation or reduction reaction to produce the biological impact of a luminescent substrate.The present invention provides at least two types of microorganisms used in the preparation of the elimination of immune privilege of drugs in cells or tissues, where they accumulate in the cells of the immune privilege, so that the animal against the immune cells or tissue autoimmune exemption. Reduction of flavin mononucleotide (substrate) then with oxygen (activator) and bacterial luciferase reaction, the formation of an intermediate state flavin peroxide, which undergo further reaction in the presence of long chain aldehydes to produce light conditions .continue to apply (continuation) 10 / 189,918; the name of the invention, May 19, 2004 to apply for the "for the diagnosis and treatment of light-emitting microorganisms and cell tissue trauma or inflammation-related diseases," the U. 01 125 911.6,2001 application on October 30 , title of the invention is "for tumor diagnosis and treatment of light-emitting microorganisms and cells"; EP 632.6,2004 Application No. F3 genes encoding proteins contemplated herein and SEQ ID No: 2 shown in the full-length amino acid sequence typically having at least about 50%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 85 %, at least about 90%, at least about 93%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% identity.020,794, filed January 28, entitled "the process for the diagnosis and treatment of tumors and microbial cells" ;. 02 012 552.2,2002 application on June 5, invented the name "for the diagnosis and treatment of inflammatory tissue associated with trauma or disease-emitting microorganisms and cells" When enabled, the full text of these applications and the reference. The present invention also includes other viruses corresponding loci, leading to when it is modified to reduce or eliminate toxicity when and / or enhanced accumulation in tumors (and non-tumor cells, tissues and organs relative ratio).与LIVP中F3基因相等同的其他病毒中的相应基因座可以通过病毒基因组中基因的结构定位确定：LIVP F3基因位于痘苗病毒的Hind III-F片段上，在开放读框F14L和F15L之间，由Goebel et al.，Virology(1990)179：247-266阐明，并且与ORFs F14L和F15L的方向相反；因此本发明包括其他病毒如痘病毒包括正痘病毒(orthopoxvirus)中的相应基因座。 With LIVP F3 gene in other viruses equivalent to the corresponding locus by the viral genome structural gene location determination: LIVP F3 gene is located on the Hind III-F fragment of vaccinia virus between open reading frames F14L and F15L, by .For example, in a study to carry non-metastatic colon cancer in nude mice injected systemically modified vaccinia virus WR strain, the modified vaccinia virus growth factor is a deletion and insertion of the thymidine kinase locus enhanced green fluorescent protein . As used herein, a microorganism with low toxicity means that on the basis of the given microorganism, the microorganism in the organs and tissues of the host does not accumulate to the extent that cause organ damage or injury or survival of the host is higher than the disease being treated degree of influence on the survival of the host.The treatment of the disease is one of the target tissue and / or cells are immune disease exemption (immunoprivileged), and the target tissue and / or cells, and usually their local environment to some extent, it is difficult to escape the immune system or close to the immune system. As used herein, animals include any animal, such as, but not limited to, primates, including humans, apes and monkeys; rodents, such as mice and rats; poultry, such as chickens; ruminants, such as goats, cattle, deer, sheep; and other animals, including pigs, horses, cats, dogs and rabbits.The microorganisms are designed to accumulate in immunoprivileged tissues and cells, such as in tumors and other proliferating tissue and in inflamed tissues, compared to other tissues, cells and organs, so that they exhibit relatively low toxicity to host organisme. Throughout this disclosure of all patents, patent applications, published applications and publications, website and other material published unless otherwise specified are incorporated by reference in their entirety.
The microorganism is not selected according to their ability to rapidly lyse the cells, but according to their accumulation in tumor cells such as immune privilege in an amount sufficient to cause leakage of the antigen for a sufficient length of time to stimulate an immune response and the ability to choose. As used herein, a delivery vehicle for administration refers to a lipid-based composition or other polymers, such as liposomes, micelles or reverse micelles, a microorganism associated with active substances such as the present invention provides for delivery to the host animal.
The present invention further provides elimination of animal immune cells such as tumor cells process (and the application of the microorganism) exemption, the method of the pharmaceutical composition is administered to an animal, whereby the virus accumulates in immune privilege of the cells, by This mediated autoimmunity, resulting in the elimination or reduction of the cell number. Computer Analysis of Sequence Data, Part I, Griffin, AM, and Griffin, HG, eds, Humana Press, New Jersey, 1994; Sequence Analysis in Molecular Biology, von Heinje, G., Academic Press, 1987; and Sequence Analysis Primer, Gribskov, Devereux, J., eds, M Stockton Press, New York, 1991; Carillo et al (1988) SIAM JApplied Math 48:. Nucleic acid molecule is typically substantially homologous full-length sequences under moderately stringent or highly stringent conditions to a nucleic acid of interest, or at least about 70%, 80% or 90% sequence hybridize.任两个核酸分子是否具有至少80％、85％、90％、95％、96％、97％、98％或99％的核苷酸序列“相同性”，可以使用已知计算机算法如FASTA程序使用例如默认参数确定，如Pearson et al.(1988)Proc. As used herein, refers to the light emitting detectable EM radiation, generally when the UV energy of the excited state product release chemical processes generated when accompanied by light emission and restore its ground state, IR or visible EM radiation.