CN109097366A - People 2Ig-B7-H3 protein coding gene, recombinant vector, its pharmaceutical composition and its application of mutation - Google Patents
People 2Ig-B7-H3 protein coding gene, recombinant vector, its pharmaceutical composition and its application of mutation Download PDFInfo
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70532—B7 molecules, e.g. CD80, CD86
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
The present invention relates to genetic engineering field, in particular to people's 2Ig-B7-H3 protein coding gene of a kind of mutation, albumen, recombinant vector, and the pharmaceutical composition including the gene or albumen.The albumen of coded by said gene of the invention, modulated expression, interaction and signal play an important role during being delivered in tumor immune response, and in particular prevention and treatment cancer provides advantageous new way.
Description
Technical field
The present invention relates to genetic engineering field, in particular to a kind of people 2Ig-B7-H3 protein coding gene, its coding
Enzyme, recombinant vector, its pharmaceutical composition and application.
Background technique
The activation of T cell needs two different signals.First signal is mutual from TCR and Antigenic Peptide-MHC compound
Effect, B7 family molecule of the second signal on APC combine generation with its ligand CD28 family molecule on T cell
Costimulatory signal, such as B7-1B7-2 and CD28, CTLA-4 is combined, which is referred to as classical B7 approach.
Human B 7-H 3 gene is found in the cDNA library of human dcs by Chapoval etc. first, due to
Its structure therefore is named as B7Homolog 3 similar to the gene of B7 family, abbreviation B7-H3.It is a kind of I type transmembrane glycoprotein,
Contactin, 20-27%'s is homologous extracellularly having with other members of B7 family on amino acid sequence
Property.
B7-H3 has extensive expression: being expressed in most of tissues in transcriptional level B7-H3, the only table on protein level
Such as human liver, lung, bladder, testis, prostate, breast, placenta and lymphoid organ are organized up in minority；B7-H3 is in gene
(mRNA) difference expressed on horizontal and protein level may be related with the post-transcriptional control of molecule.
B7-H3 is one immune in addition to that can regulate and control lymphopoiesis during the humoral immunity of antigentic specificity
Regulatory molecule, find that it also has important clinical meaning in many tumour cells again in recent years: i.e. it is thin in many tumours
There is high expression in born of the same parents, it may be possible to the regulatory factor of a tumor resistance.
The human B 7-H 3 assignment of genes gene mapping is on No. 15 chromosomes, and there are two types of various forms of spliced bodies in vivo for albumen: 2IgB7-
H3 and 4IgB7-H3.2IgB7-H3 extracellular fragment is made of two immunoglobulin domains of IgV-IgC.It is intended that by grinding
Study carefully discovery, the gene mutation and the correlation of tumor resistance of 2IgB7-H3.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of people 2Ig-B7-H3 protein coding genes, enzyme, again of its coding
Group carrier, its pharmaceutical composition and application, the people 2Ig-B7-H3 protein coding gene provide new way to the treatment of cancer
Diameter.
The invention discloses a kind of people's 2Ig-B7-H3 protein coding genes of mutation, and the gene is:
(1) nucleotide sequence shown in SEQ ID NO:1.
The invention discloses a kind of people 2Ig-B7-H3 albumen, the encoding gene of the people 2Ig-B7-H3 albumen is described prominent
People's 2Ig-B7-H3 protein coding gene of change.
The invention discloses a kind of recombinant vector, the recombinant vector includes the target gene of carrier and its carrying, described
Target gene is people's 2Ig-B7-H3 protein coding gene of mutation described in above-mentioned technical proposal.
Preferably, the carrier is selected from by cloning vector, carrier for expression of eukaryon, prokaryotic expression carrier and shuttle vector.
The invention discloses a kind of pharmaceutical composition, described pharmaceutical composition includes excipient and the above-mentioned technical side of selection
One or more of people 2Ig-B7-H3 albumen and the recombinant vector described in case.
Preferably, described pharmaceutical composition is injection, the injection include pharmaceutically acceptable excipient and
Selected from one or more of recombinant vector described in above-mentioned technical proposal.
The invention discloses the people 2Ig-B7-H3 protein coding gene of mutation described in above-mentioned technical proposal preparation prevention and
Application in the drug for the treatment of cancer.
Compared with prior art, the present invention provides a kind of people's 2Ig-B7-H3 protein coding gene of mutation, albumen, weights
Group carrier, and the pharmaceutical composition including the gene or albumen.The albumen of coded by said gene of the invention, modulability table
It reaches, interact and signal is delivered in during tumor immune response and plays an important role, in particular prevent and control
It treats cancer and provides advantageous new way.
Specific embodiment
The exemplary embodiment of the disclosure is described in more detail below.The exemplary embodiment of the disclosure can be with various
Form is realized the disclosure and be should not be limited by the embodiments set forth herein.It is to be able to more on the contrary, providing these embodiments
Thoroughly understand the disclosure, and the scope of the present disclosure can be fully disclosed to those skilled in the art.
The embodiment provides a kind of people's 2Ig-B7-H3 protein coding genes of mutation, and the gene is:
(1) nucleotide sequence shown in SEQ ID NO:1.
The people 2Ig-B7-H3 protein coding gene of the mutation includes 2765 bases altogether, is located at 5 ' the 1488th alkali in end
C > T heterozygous mutant occurs for base.
The invention discloses a kind of people 2Ig-B7-H3 albumen, the encoding gene of the people 2Ig-B7-H3 albumen is described prominent
People's 2Ig-B7-H3 protein coding gene of change.
Embodiment of the invention discloses a kind of recombinant vector, the recombinant vector includes the purpose base of carrier and its carrying
Cause, the target gene are people's 2Ig-B7-H3 protein coding genes of mutation described in above-mentioned technical proposal.
Wherein, the target gene can also include regulating and controlling sequence, such as one or more of destination gene expression
Promoter, terminator and enhancer.The target gene also may include marker gene (for example, coding beta-galactosidase, green
The gene of color fluorescin or other fluorescins) or its product adjust the gene of other gene expressions.The target gene removes
It can be outside DNA, can also be mRNA, tRNA or rRNA, can also include associated retroviral tune usually relevant to transcription sequence
Control sequence, such as transcription stop signals, site of polyadenylation and downstream enhancer elements.
It is improved that the carrier can be the various carriers that can carry target gene and technology development commonly used in the art
The available various carriers that can carry target gene.The carrier is for example, plasmid (naked DNA), liposome, molecule couple body, more
Polymers and virus.
The plasmid (naked DNA) can carry target gene, this carry target gene plasmid can with direct injection or
It is imported into histocyte by particle gun, electroporation and electro fusion.In addition, ultrasonic wave helps to improve the transfer of plasmid
Efficiency.Ultrasonic wave cooperates microvesicle echo that permeability of cell membranes can be improved than poor agent, to significantly improve transfer and the table of naked DNA
Up to efficiency.This after birth infiltration technology can manufacture aperture in cell membrane surface moment, and DNA then takes advantage of the occasion to enter intracellular.
The particle that the liposome is made of lipid bilayer can mediate target gene to pass through cell membrane.The rouge
Matter can be the natural phospholipid based on lecithin (phosphatidyl choline, PC) from yolk and soybean；It is also possible to two palm fibres
Palmitic acid phosphatidyl choline (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), Distearoyl Phosphatidylcholine (DSPC) etc. are closed
At phosphatide；Cholesterol can also be contained.Preferred liposome is cationic-liposome, mainly by positively charged lipid and in
Property helper lipid is mixed with equimolar.It can be effectively formed between the positively charged liposome and negatively charged DNA
Compound, and moved into the cell by endocytosis.
The polymer utilizes Cationic conjugated polymers, such as bearing on the positive charge and DNA on poly-l-lysine
Charge bonded occurs electrically to neutralize guanidine, and forms stable polymer/DNA compound.Gained Cationic conjugated polymers and DNA's answers
It is still positively charged to close object, in conjunction with receptor that can be negatively charged with cell surface, and is infiltrated to intracellular.
The molecule couple body be the exogenous DNA of target gene is covalently bound to specific cell surface receptors aglucon or
In monoclonal antibody or viral membrane-associated protein, using special binding characteristic introducing exogenous channel genes to certain types of thin
In born of the same parents.
Virus usually can expeditiously enter specific cell, express oneself protein, generate new virion, therefore
The virus being modified becomes the carrier of gene therapy first.For example, retrovirus vector, adenovirus vector, gland related diseases
Poisonous carrier and herpes simplex virus vector etc..Wherein, the adeno-associated virus belong to the Parvoviridae family of non-pathogenic at
Member only is likely to be proliferated dependent on helper virus.Adeno-associated virus genome very little, such as 2 type adeno-associated virus are by 4681
The single stranded DNA of a nucleotide composition, includes 2 genes, i.e., rep gene (be responsible for adjusting virus replication, expression of structural gene by coding
With the albumen being integrated into host genome) and cap gene (coding capsid structural protein), there are 1 for 1 end of genome
The terminal repeat of 145bp.Adeno-associated virus can infect division stage and stationary phase cells, can be inserted into host cell chromosome
It is interior, or expressed steadily in the long term in the form of concatermer DNA outside chromosome, can effectively transduce the types such as brain, skeletal muscle and liver
Cell, have the characteristics that antigenicity, small toxicity and not pathogenic.
Preferably, the carrier is selected from by cloning vector, carrier for expression of eukaryon, prokaryotic expression carrier and shuttle vector.
Embodiment of the invention discloses a kind of pharmaceutical composition, described pharmaceutical composition includes in excipient and selection
State one or more of people 2Ig-B7-H3 albumen and the recombinant vector described in technical solution.
The excipient that the drug receives refer to nontoxic solid-state, semisolid or liquid filler, diluent, coating material or its
His pharmaceutical adjunct, it may for example comprise but it is not limited to salt water, buffering saline solution, glucose, water, glycerol, ethyl alcohol and its mixture.It is described
Pharmaceutical composition is suitable in parenteral, sublingual, brain pond, in intravaginal, peritonaeum, in rectum, cheek is interior or Epidermal administration.
Parenteral includes in intravenous, intramuscular, peritonaeum, in breastbone, subcutaneous, intra-articular injection and infusion.Suitable for stomach
The pharmaceutical composition of parenteral administration includes aseptic aqueous solution or non-aqueous solution, dispersion liquid, suspension or lotion, and for facing
Use the preceding powder prepared in sterile injectable solution or dispersion liquid.Suitable aqueous or non-aqueous carrier, diluent, solvent
Or excipient includes the organic ester of water, ethyl alcohol, glycerol, propylene glycol, polyethylene glycol, carboxymethyl cellulose, vegetable oil and injectable
Such as ethyl oleate.These compositions can also contain preservative, wetting agent, emulsifier, protective agent and dispersing agent adjuvant, such as flesh
Alcohol, sorbierite and sucrose.It is preferably added to osmotic pressure regulator such as carbohydrate, sodium chloride, potassium chloride.
Epidermal administration includes being administered on skin, mucous membrane and in lung and eye surface.Such pharmaceutical composition includes powder
Agent, ointment, drops, transdermal patch, Iontophoretic device and inhalant etc..The composition of rectum or vagina administration is preferred
For suppository, it can by by recombinant vector of the invention and suitable non-irritating excipient such as cocoa butter, polyethylene glycol or
Suppository wax is mixed with, and it is under body temperature liquid, therefore in rectum or vaginal canal that the excipient or carrier, which are solid-state in room temperature,
Interior fusing simultaneously releases reactive compound.
Preferably, described pharmaceutical composition is injection, the injection include pharmaceutically acceptable excipient and
Selected from one of human glocose kinase mutants encoding gene of the present invention and recombinant vector of the present invention or several
Kind.
Preferably, described pharmaceutical composition is injection, the injection include pharmaceutically acceptable excipient and
Selected from one or more of recombinant vector described in above-mentioned technical proposal.
Embodiment of the invention discloses the people 2Ig-B7-H3 protein coding genes of mutation described in above-mentioned technical proposal to make
Application in the standby drug for preventing and treating cancer.
The above description of the embodiment is only used to help understand the method for the present invention and its core ideas.It should be pointed out that pair
For those skilled in the art, under the premise of not departing from this bright principle, if can also be carried out to the present invention
Dry improvement and modification, these improvements and modifications also fall within the scope of protection of the claims of the present invention.
The foregoing description of the disclosed embodiments enables those skilled in the art to implement or use the present invention.
Various modifications to these embodiments will be readily apparent to those skilled in the art, as defined herein
General Principle can be realized in other embodiments without departing from the spirit or scope of the present invention.Therefore, of the invention
It is not intended to be limited to the embodiments shown herein, and is to fit to and the principles and novel features disclosed herein phase one
The widest scope of cause.
Claims (7)
1. a kind of people's 2Ig-B7-H3 protein coding gene of mutation, which is characterized in that the gene is:
(1) nucleotide sequence shown in SEQ ID NO:1.
2. a kind of people 2Ig-B7-H3 albumen, which is characterized in that the encoding gene of the people 2Ig-B7-H3 albumen is claim 1
People's 2Ig-B7-H3 protein coding gene of the mutation.
3. a kind of recombinant vector, the recombinant vector includes the target gene of carrier and its carrying, which is characterized in that the purpose
Gene is people's 2Ig-B7-H3 protein coding gene of mutation described in claim 1.
4. recombinant vector according to claim 3, which is characterized in that the carrier is selected from by cloning vector, eukaryotic expression
Carrier, prokaryotic expression carrier and shuttle vector.
5. a kind of pharmaceutical composition, which is characterized in that described pharmaceutical composition includes described in excipient and selection claim 2
One or more of recombinant vector described in people 2Ig-B7-H3 albumen and claim 3~4 any one.
6. pharmaceutical composition according to claim 5, which is characterized in that described pharmaceutical composition is injection, the note
Penetrating liquid includes pharmaceutically acceptable excipient and selected from one or more of recombinant vector described in claim 3 or 4.
7. the people 2Ig-B7-H3 protein coding gene of mutation described in claim 1 is in the drug that preparation prevents and treats cancer
Application.
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| WO2024148521A1 (en) * | 2023-01-10 | 2024-07-18 | 周田弘 | Recombinant human 2ig-b7-h3 protein-coding gene, recombinant vector, host cell, pharmaceutical composition and use thereof |
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| WO2024148521A1 (en) * | 2023-01-10 | 2024-07-18 | 周田弘 | Recombinant human 2ig-b7-h3 protein-coding gene, recombinant vector, host cell, pharmaceutical composition and use thereof |
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