CN103819559B - The purposes of a kind of anti-mesothelin nano antibody and encoding gene and this nano antibody - Google Patents
The purposes of a kind of anti-mesothelin nano antibody and encoding gene and this nano antibody Download PDFInfo
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- CN103819559B CN103819559B CN201310667427.2A CN201310667427A CN103819559B CN 103819559 B CN103819559 B CN 103819559B CN 201310667427 A CN201310667427 A CN 201310667427A CN 103819559 B CN103819559 B CN 103819559B
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Abstract
The invention discloses a kind of nano antibody of anti-mesothelin and the purposes of encoding gene and this nano antibody thereof, it relates to a kind of nano antibody of antitumor differentiation antigen and the purposes of encoding gene and this nano antibody thereof.Is the amino acid of the nano antibody of anti-mesothelin provided by the invention as SEQ? ID? shown in NO:2.Is the nucleotide sequence of the nano antibody encoding gene of anti-mesothelin as SEQ? ID? shown in NO:1.The probe of high expression level mesothelin cancer cells or the medicine of preparation suppression high expression level mesothelin cancer cells is prepared with the nano antibody of anti-mesothelin.Nano antibody mesnab1 of the present invention can the mesothelin of specific binding tumor cell surface expression, can be used for treating and the tumour of diagnosis mesothelin high expression level, and the effect of research mesothelin in tumour occurs.The present invention can be applicable to biology, medical field.
Description
Technical field
The present invention relates to a kind of nano antibody of antitumor differentiation antigen and the purposes of encoding gene and this nano antibody thereof.
Background technology
Mesothelin (mesothelin, MSLN) is newfound a kind of Tumor Differentiation antigen in recent years.Its precursor is glycophospholipin acyl-glycero (GPI) grappling, glycosylated cells surface protein; can be the N-terminal secretion type albumen of 31kD and the C-terminal protein of 40kD by furin protease hydrolysis; the latter mainly exists with the form of membrane-bound GPI grappling; limitedly be distributed in normal rnesothelial cells and superficial epithelial cells, therefore called after mesothelin.
Mesothelin is limited expression in the normal tissue, and in some tumour high expression level, as carcinoma of the pancreas (100% case), adenocarcinoma ovaries (case of 70%), adenocarcinoma of lung (case of 50%) and malignant mesothe (case of 100%) etc.The mechanism that mesothelin induced tumor occurs may comprise following three aspects:
The first, mesothelin can promote peritoneal seeding and the transfer of tumour cell by interacting with Mucin1 6 (i.e. CA125);
The second, mesothelin promotes survival and the propagation of tumour cell by NF-κ B signal path;
3rd, the expression of mesothelin can strengthen the tolerance of tumour cell to some specific medicine (as: TNF-α, taxol, platinum-endoxan mixture).
As can be seen here, mesothelin is an ideal targets for oncotherapy.
Summary of the invention
Mesothelin, as a kind of ideal targets for oncotherapy, the invention provides a kind of nano antibody of antitumor differentiation antigen and the purposes of encoding gene and this nano antibody thereof.
The amino acid of the nano antibody of the anti-mesothelin of the present invention is as shown in SEQIDNO:2.
The nucleotide sequence of the nano antibody encoding gene of above-mentioned anti-mesothelin is as shown in SEQIDNO:1.
The probe of high expression level mesothelin cancer cells is prepared with the nano antibody of above-mentioned anti-mesothelin.
The medicine of high expression level mesothelin cancer cells is suppressed with the nano antibody preparation of above-mentioned anti-mesothelin.
The nano antibody of the anti-mesothelin of the present invention is named as nano antibody mesnab1.Nano antibody mesnab1 can the mesothelin of specific binding tumor cell surface expression, by restraining effect such as the migrations to tumour cell for the treatment of high expression level mesothelin cancer.
Nano antibody mesnab1 of the present invention can be used for the tumour (as carcinoma of the pancreas, adenocarcinoma ovaries, adenocarcinoma of lung and malignant mesothe) treating and diagnose mesothelin high expression level, and the effect of research mesothelin in tumour occurs.
Nano antibody mesnab1 molecular weight of the present invention, about 15kD, therefore has better tissue permeability, and the ability in conjunction with the spatially epitope of presence bit inhibition effect is also stronger.So, nano antibody mesnab1 of the present invention can be used for the treatment of the tumour of mesothelin high expression level as oral medicine.
Nano antibody mesnab1 of the present invention has the binding ability with FcRn, and plasma half-life reaches 10h.
Nano antibody mesnab1 of the present invention can express at prokaryotic expression system, has the advantage that production cost is low, the cycle is short.
Accompanying drawing explanation
Fig. 1 is that in embodiment 3, nano antibody mesnab1 and mesothelin are in conjunction with ELISA measurement result figure, and in Fig. 1, " ■ " curve is nano antibody mesnab1, and in Fig. 1, "●" curve is negative control antibody m01s;
Fig. 2 is the Proliferation of Human Ovarian Cell SK-OV-3 cell light field observation figure of hatching altogether with nano antibody mesnab1 in embodiment 4;
Fig. 3 is the Proliferation of Human Ovarian Cell SK-OV-3 cell TexasRed fluoroscopic examination figure of hatching altogether with nano antibody mesnab1 in embodiment 4;
Fig. 4 is the Proliferation of Human Ovarian Cell SK-OV-3 cell DAPI staining examine figure of hatching altogether with nano antibody mesnab1 in embodiment 4;
Fig. 5 is the Proliferation of Human Ovarian Cell SK-OV-3 cell light field observation figure of hatching altogether with antibody m01s in embodiment 4;
Fig. 6 is the Proliferation of Human Ovarian Cell SK-OV-3 cell TexasRed fluoroscopic examination figure of hatching altogether with antibody m01s in embodiment 4;
Fig. 7 is the Proliferation of Human Ovarian Cell SK-OV-3 cell DAPI staining examine figure of hatching altogether with antibody m01s in embodiment 4;
Fig. 8 is embodiment 5 flow cytometry detection figure.
Embodiment
Illustrate the present invention below in conjunction with specific embodiment, technical solution of the present invention is not limited to following cited embodiment, also comprises the arbitrary combination between each embodiment.
Embodiment one:
The amino acid of the nano antibody of the anti-mesothelin of present embodiment is as shown in SEQIDNO:2.
The nano antibody of the anti-mesothelin of present embodiment can be used for the treatment of high expression level mesothelin cancer, comprises carcinoma of the pancreas, adenocarcinoma ovaries, adenocarcinoma of lung and malignant mesothe etc.
The nano antibody of the anti-mesothelin of present embodiment can be used as probe, for detecting the tumour of high expression level mesothelin, as carcinoma of the pancreas, adenocarcinoma ovaries, adenocarcinoma of lung and malignant mesothe etc.
The nano antibody of the anti-mesothelin of present embodiment can also with self or other peptide fusion, for treatment and the detection of high expression level mesothelin cancer.
The nano antibody of the anti-mesothelin of present embodiment and other molecule coupling, include but are not limited to radio isotope and toxin, forms treatment and detection that coupled antibody is used for high expression level mesothelin cancer.
Present embodiment nano antibody mesnab1 has higher resistant to aggregation ability.
Present embodiment nano antibody mesnab1 introduces a pair disulfide linkage, and therefore stability is high, and its Tm value is not less than 80 DEG C.Present embodiment nano antibody mesnab1 has more excellent solubility expression and protease resistant.
Embodiment two:
The nucleotide sequence of the nano antibody of the anti-mesothelin of present embodiment is as shown in SEQIDNO:1.
The nucleotide sequence of the nano antibody of the anti-mesothelin of present embodiment is synthesized by bio-engineering corporation.
Embodiment 1.
Obtain the gene of nano antibody mesnab1 by SEQIDNO:1 synthetic, be cloned in prokaryotic expression carrier pComb3, be transformed in E.coliHB2151; Inoculate bacterial classification in the SB substratum containing 100 μ g/ml ammonia benzyls (containing 30g Tryptones, 20g yeast extract and 10gMOPS in 1L substratum, pH value NaOH is adjusted to 7.0) in, when OD600 reaches 0.7 ~ 1.0, adding IPTG to final concentration is 200 μ g/ml, in 37 DEG C, carry out abduction delivering 14 ~ 16h under the condition of 220r/min; Then at 4 DEG C, 15min collected by centrifugation thalline under 6000r/min condition, abandon substratum, precipitation is resuspended in BufferA (50mMTris-HCl, 450mMNaCl, pH8.0) in, then after PXB (polymyxinB) processes 1 hour collected by centrifugation supernatant; With Ni-NTA resin (QIAGEN company) purified nanotubes antibody mesnab1.
Embodiment 2.
Verify that the purity of nano antibody mesnab1 is more than 98% through SDS-PAGE.Be ultra-filtration centrifuge tube (MerckMillipore company) the ultrafiltration and concentration nano antibody mesnab1 of 3kD subsequently with molecular weight cut-off.The C-end of the nano antibody mesnab1 obtained for vector expression with pComb is containing 6 × His label and FLAG label.
Embodiment 3.
Mesothelin (2 μ g/mL) is coated on elisa plate, after 4 DEG C of overnight incubation, uses PBS+3%milk in 37 DEG C of closed 1h.Add the nano antibody mesnab1 of different weaker concn, 37 DEG C hatch 2 hours after wash four times with PBST (PBS+0.05%Tween20), add after mouse-anti FLAG monoclonal antibody that horseradish peroxidase (HRP) marks hatches 1 hour in 37 DEG C again, wash four times with PBST, then add ABTS and detect.And with antibody m01s (GongR, etal., JBiolChem., 2011) as negative control.
The EC50 that nano antibody mesnab1 and mesothelin combine is 273nM, and antibody m01s can not combine (as shown in Figure 1) with mesothelin.ELISA experiment proves that nano antibody mesnab1 can combine with antigen mesothelin.
Embodiment 4.
By the SK-0V-3 (5 × 10 of 500 μ L
5~ 6 × 10
5individual/ml) cell inoculates 24 orifice plates, and add nano antibody mesnab1 after cultivating 14 ~ 16h, hatch 2 hours for 37 DEG C; PBSA (PBS+0.5%BSA), PBS is used to add after cleaning 3 times respectively afterwards after fluorescence two anti-(sheep anti-mouse igg of TexasRed coupling) hatches 1h in 37 DEG C, the staining conditions washing observation of cell under fluorescent microscope after 3 times is cleaned again respectively with PBSA, PBS, and using antibody m01s as negative control.
DAPI dyeing is in order to the existence of indicator cells core.According to Fig. 2 ~ Fig. 7, the Proliferation of Human Ovarian Cell SK-OV-3 cell of hatching altogether with nano antibody mesnab1 is by red-dyed, and SK-OV-3 has been proved to be able to high expression level mesothelin, show that nano antibody mesnab1 can be combined with the mesothelin of Proliferation of Human Ovarian Cell SK-OV-3 cell surface expression.As negative control, antibody m01s does not detect the combination with mesothelin.
Embodiment 5.
Get SK-OV-3 cell (about 1 × 10
6individual), hatch 2 hours with nano antibody mesnab1 at 37 DEG C, after cleaning 3 times respectively with PBSA, PBS, add mouse-anti FLAG monoclonal antibody, hatch 1 hour for 37 DEG C; Fluorescence two anti-(sheep anti-mouse igg of TexasRed coupling) is added, after hatching 1h in 37 DEG C, in analyzing on flow cytometer after cleaning 3 times respectively with PBSA, PBS afterwards after cleaning 3 times respectively with PBSA, PBS again.And using antibody m01s as negative control.
As shown in Figure 8, the fluorescence adding the SK-OV-3 cell of nano antibody mesnab1 has significant migration, has confirmed the conclusion of embodiment 4 immunofluorescent staining.Illustrate that nano antibody mesnab1 is inhibited to high expression level mesothelin cancer cells simultaneously.
The present invention is not limited to above-mentioned preferred forms, and anyone should learn the structural changes made under enlightenment of the present invention, and every have identical or close technical scheme with the present invention, all falls within protection scope of the present invention.
Claims (4)
1. a nano antibody for anti-mesothelin, is characterized in that the amino acid of described nano antibody is as shown in SEQIDNO:2.
2. the encoding gene of the nano antibody of anti-mesothelin as claimed in claim 1, is characterized in that the nucleotide sequence of described gene is as shown in SEQIDNO:1.
3. the purposes of the nano antibody of anti-mesothelin as claimed in claim 1, is characterized in that the probe preparing high expression level mesothelin cancer cells with the nano antibody of anti-mesothelin.
4. the purposes of the nano antibody of anti-mesothelin as claimed in claim 1, the nano antibody preparation that it is characterized in that with anti-mesothelin suppresses the medicine of high expression level mesothelin cancer cells.
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Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20240124563A1 (en) * | 2020-12-09 | 2024-04-18 | Nanjing Zaiming Pharmaceutical Co., Ltd. | Anti-Human MSLN Antibody And Application Thereof |
| CN114685667B (en) * | 2020-12-28 | 2024-04-12 | 浙江纳米抗体技术中心有限公司 | Mesothelin binding molecules and uses thereof |
| CN114685666B (en) * | 2020-12-28 | 2023-10-03 | 浙江纳米抗体技术中心有限公司 | Anti-mesothelin nanobody and application thereof |
| EP4269442A1 (en) * | 2020-12-28 | 2023-11-01 | Zhejiang Nanomab Technology Center Co. Ltd. | Mesothelin binding molecule and application thereof |
| CN115991782A (en) * | 2021-10-18 | 2023-04-21 | 普米斯生物技术(珠海)有限公司 | Anti-mesothelin nanobody and use thereof |
| CN116063530B (en) * | 2021-12-29 | 2023-09-29 | 华道(上海)生物医药有限公司 | Antibody for resisting mesothelin and application thereof |
| WO2023131276A1 (en) * | 2022-01-06 | 2023-07-13 | 原启生物科技(上海)有限责任公司 | Antigen binding protein targeting msln and use thereof |
| WO2023179740A1 (en) * | 2022-03-25 | 2023-09-28 | Shanghai Henlius Biotech , Inc. | Anti-msln antibodies and methods of use |
| WO2024088371A1 (en) * | 2022-10-28 | 2024-05-02 | 原启生物科技(上海)有限责任公司 | Antigen-binding protein targeting msln |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101563454A (en) * | 2006-12-08 | 2009-10-21 | 株式会社免疫生物研究所 | Diagnostic agent for mesothelioma, diagnosis kit for mesothelioma, and diagnosis method for mesothelioma |
| CN101951946A (en) * | 2007-10-01 | 2011-01-19 | 百时美施贵宝公司 | Human antibodies that bind mesothelin, and uses thereof |
| CN101952319A (en) * | 2007-11-26 | 2011-01-19 | 拜耳先灵制药股份公司 | Anti-mesothelin antibodies and uses therefor |
-
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101563454A (en) * | 2006-12-08 | 2009-10-21 | 株式会社免疫生物研究所 | Diagnostic agent for mesothelioma, diagnosis kit for mesothelioma, and diagnosis method for mesothelioma |
| CN101951946A (en) * | 2007-10-01 | 2011-01-19 | 百时美施贵宝公司 | Human antibodies that bind mesothelin, and uses thereof |
| CN101952319A (en) * | 2007-11-26 | 2011-01-19 | 拜耳先灵制药股份公司 | Anti-mesothelin antibodies and uses therefor |
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