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Field of the invention provides a microorganism comprising an attenuated or modified (microorganism) (including microorganisms (microbe) and cell) vaccine, and methods for preparing the microorganisms and vaccines of the present invention. Goebel et al, Virology (1990) 179: 247-266 elucidated, and contrary to the direction of ORFs F14L and F15L; Accordingly the present invention include other viruses such as poxviruses including orthopoxviruses (orthopoxvirus) corresponding locus.
In particular, the present invention provides a modified bacterial, viral and eukaryotic cells and for the treatment of proliferative and inflammatory disorders and methods give the product in tumors used. As used herein, attenuated (attenuate) the toxicity of a microorganism refers to a given microorganism is not attenuated compared to reduce or eliminate deleterious or toxic effects when administered to the host microorganism.
Said method comprising administering (typically for systemic administration) A microorganism, the microorganisms preferentially accumulate in cells such as immune privilege of tumor cells, leading to proteins and other compounds such as tumor antigen leakage, resulting in a host, such as a tumor antigen against non-host proteins immunity, thereby eliminating the exemption immune cells such as tumor cells through the immune system of the host. For example, the compounds produced in the tumor can be, for example metabolite, or a polypeptide encoded by RNA, or a compound represented by the recombinant polypeptide (e.g., an enzyme), and tumor cell or immune system cells or tissues exemption produced.
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 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 product comprises a detectable protein or may produce a detectable signal, such that the distribution and monitoring of treatment efficacy can be monitored given microorganism, because when the immune privilege of the cells are eliminated when the microorganism is eliminated. Computational Molecular Biology, Lesk, AM, ed, Oxford University Press, New York, 1988; Biocomputing:. USA 85：2444所述(其他程序包括GCG程序包(Devereux，J.，et al.，Nucleic Acids Research 12(I)：387(1984))、BLASTP、BLASTN、FASTA(Atschul，SF，et al.，J Molec Biol 215：403(1990))；Guide to Huge Computers，Mrtin J. Conditions conducive to synthesis include the presence of nucleoside triphosphates such as used in the polymerization and the active material and extending, such as DNA polymerase, and a suitable buffer, temperature and p H.
The pharmaceutical compositions may be formulated for any mode of administration, the mode of administration, including, but not limited to systemic administration, such as intravenous administration. Informatics and Genome Projects, Smith, DW , ed, Academic Press, New York, 1993;.. Bishop，ed.，Academic Press，San Diego，1994，及Carillo et al.(1988)SIAM J Applied Math48：1073)。 Whether any two nucleic acid molecules having at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% nucleotide sequence "identity", using known computer algorithms such as FASTA program for example, the default parameters determined, e.g. As used herein, chemiluminescence refers to a chemical reaction in which energy is specifically directing molecule, resulting in it becomes electronically excited state and subsequent release of photons, and thus emit visible light.
Methods for making tumor specific antibodies and also methods of making gene products encoded by the microorganism as well as antibodies reactive therewith are provided. The recombinant vaccinia virus according to any one of the preceding claims, wherein the heterologous nucleic acid encodes a detectable protein or capable of inducing a detectable signal protein. An animal cells of the immune privilege eliminate, comprising administering to the animal a pharmaceutical composition of claim 18 or 19, whereby the virus accumulates in immune privilege of the cells, thereby mediating autoimmunity, resulting in elimination of the cell or reduce the number. The method of claim 20, wherein: the pharmaceutical composition comprises a vaccinia virus Lister strain, the Lister strain comprising a modified TK and HA gene and optionally F3 gene or locus containing modifications thereof; and the resulting virus in non-targeted organs do not accumulate to toxic levels. A method of treatment to eliminate the exemption animal immune cells or tissue, comprising: administering to the animal a microorganism, wherein: the microbial cells accumulate in immune privilege; the microbes in the animal's organs and tissues unaffected in does not accumulate and has a low toxicity; immune privilege of the microbial cell membrane resulting in leakage of the cell, so that the animals against the cells or cell products of autoantibodies. A microorganism used in pharmaceutical formulations for the elimination of animal immune privilege in the cells or tissues, wherein: the microbial cells accumulate in immune privilege; the microorganism is not included in the exemption immune cells or tissues organs and tissues does not accumulate to toxic levels. Microorganism of the present invention is provided with respect to the wild-type and typical modified to present one or more characteristics such as reduced pathogenicity, reduced toxicity, relative to normal tissues and organs and preferentially accumulate in tumors, increasing the immunogen resistance, increased ability to stimulate or enhance the immune response to tumor cells, an increased ability to dissolve or kill tumor cells, decreased ability to dissolve or kill tumor cells.
1-14 and 32 according to any one of the recombinant virus, or (b) 33. Usually given a microorganism will stimulate an immune response to clear the microorganism, but immunologically privileged site is shielded or isolated with the immune system, such that the microorganisms survive and replicate normally.