CN1331885C - Tumor antigen protein and tumor antigen peptide - Google Patents
Tumor antigen protein and tumor antigen peptide Download PDFInfo
- Publication number
- CN1331885C CN1331885C CNB031360696A CN03136069A CN1331885C CN 1331885 C CN1331885 C CN 1331885C CN B031360696 A CNB031360696 A CN B031360696A CN 03136069 A CN03136069 A CN 03136069A CN 1331885 C CN1331885 C CN 1331885C
- Authority
- CN
- China
- Prior art keywords
- tumor antigen
- protein
- cell
- leu
- ile
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
Abstract
The present invention relates to tumor antigen protein and tumor antigen peptide. The tumor antigen protein can generate a peptide fragment which is combined with molecules in the major histocompatibility complex (MHC)-I class and is identified by a T cell in a combination state, and a DNA sequence for encoding the tumor antigen protein has a nucleotide sequence of a sequence with the accession number in a gene library of TPTEAF007118. The tumor antigen protein / the tumor antigen peptide can be used for preparing medicine for treating liver cancer or lung cancer.
Description
Technical field
The present invention relates to the application of a kind of tumor antigen protein matter and tumor antigen peptide, particularly relate to a kind of tumor antigen protein and antigen peptide and treating the application in liver cancer/lung-cancer medicament as tumor-testis antigen, preparation.
Background technology
Malignant tumour is a big class disease that threatens human health.Tumour be a very complicated process.The important factor that tumour cell can take place and make progress is that it can escape the supervision effect of body immune system, therefore how to excite and the tumour cell that arouses the immune system recognition of body and repel " non-oneself " composition is a breach seeking new tumor therapeuticing method.At the initial stage that the immunotherapy of tumour is studied, people have been developed a lot of ways and have been come the immunity system of excitating organism to repel the tumour cell of " non-own " composition, although these methods have obtained better curative effect in the treatment of animal tumor model, in the treatment of human tumor, still lack significant effect.
The intravital immunity system of known person comprises humoral immunization and cellular immunization, and especially T cellular immunization suppresses to play an important role to killing and wounding of tumour.Along with the understanding of people to immune response essence, it is found that no matter how complicated the process of immunne response is, finally cause the T cell activation and produce being exactly to combine and forming antigenic peptide complexes and costimulatory signal of lethal effect with major histocompatibility complex MHC, that is: cytotoxic T cell (CTL) is by the TXi Baoshouti (TCR) on self surface, the complex body that recognition expression combines with major histocompatibility complex (MHC) I class antigen and forms in the tumor antigen protein matter/peptide of tumor cell surface, thus killing tumor cell attacked.
The generation of tumor antigen protein matter/peptide is to be expressed as tumour antigen earlier by tumour cell, it is resolved into the antigen peptide of 8～10 amino acid sizes by various proteolytic enzyme in cell, these antigen peptide produce MHC I quasi-molecule with the while and combine in endoplasmic reticulum, be expressed in the surface of cell by Golgi complex, finally offer to the special CTL of tumour antigen, thereby bring out immunne response, kill and wound the removing tumour cell.The proteantigen molecule that thisly be present in the tumour cell, can combine and bring out organism immune response with the MHC molecule is tumour antigen.Can only produce a immune response with these antigen induction bodies at tumour cell, thus the intravital tumour cell of specific killing and reach the effect that treatment or control tumour cell shift.Therefore in recent decades, people are seeking on tomour specific and/or the dependency antigen with focusing on of immunization method treatment tumour.
In nineteen fifties, people such as Foley self the tumour cell immunity of the mouse that produces tumour through chemomorphosis with deactivation after, the tumour cell of living for this mouse inoculation again, these tumour cells are ostracised and can not be grown into tumour, mouse then survives; Contrast with it, behind the tumour cell that self tumour cell mice immunized inoculation of deactivation useless is lived, tumour cell is not ostracised and is grown into tumour, and mouse is then dead.This experiment has proved that with compellent evidence there is tumour specific antigen in the tumour of chemomorphosis; but this protective reaction has accurate specificity; promptly only at the tumour of same type and not at different types of tumors, even to also not having provide protection with same carcinogen dissimilar tumours of inductive on same mouse.
1991, T.Boon etc. identified tumor antigen protein matter first from human melanoma cell, and called after MAGE (science, 254:1643-1647,1991).Subsequently, people identify out some other tumor antigen protein matter again, can be divided into the tumor antigen protein matter of tumor-testis (CT) antigen protein, differentiation antigen protein, sudden change, tumor antigen protein matter and virus antigen protein five classes of expressing excessively.Wherein, being applied to is tumor-testis (CT) antigen protein clinically the most widely.
Tumor-testis (CT) antigen protein is a maximum class in the tumour antigen of identifying at present, the characteristics of their encoding genes are in the tumour of a lot of types expression to be arranged all, as expression is all arranged in melanoma, lung cancer, sarcoma and bladder cancer, but do not express in the healthy tissues except that testis, a certain amount of expression is arranged in placenta, ovary, pancreas.Because testis is immunity special permission position, so this class antigen is considered to the antigen of tumour-specific in treatment, is a class antigen that is hopeful to be used as the immunotherapy of tumors purposes most.Try out at present in clinically also mainly be exactly this class antigen, as MAGE-1 and NY-ESO-1 promptly is the expression that high positive rate is arranged in the tumour of certain type, the antigen protein that good immunogenicity is arranged again has good prospect when being used for the immunotherapy of tumour.
Up to the present, the most representative method of tumor antigen protein matter of identifying is: based on the library screening method on the specificity cellular immunity response basis, based on cDNA expression library sieve method, combined peptide library screening, sour elution method and bioinformatics method on the humoral immunoresponse(HI) basis.
Liver cancer and lung cancer are the most common and virulent tumours the most in the human tumor, and especially in the last few years, sickness rate increased gradually.They are because the grade of malignancy height, growth rapidly, in case find to be middle and advanced stage just, at present, treatment mainly is local therapeutic approaches such as traditional excision and radiotherapy, but all entered middle and advanced stage when making a definite diagnosis owing to most of patient, and radiotherapy and chemotherapy are had suitable resistivity, therefore the effect and the prognosis of treatment are often relatively poor.It is very low that a year of hepatocarcinoma patient is compared with the survival rate of other all kinds of tumour patients with five-year survival rate.Breakthrough or the new methods of treatment sought on the methods of treatment are the targets that the clinical tumor scholar pursues always, people's early diagnosis and good prognosis of patient that new method improves liver cancer and lung cancer that wait in expectation, and postoperative is removed tumour cell residual in the body and is prevented the transfer of tumour cell.
Summary of the invention
The object of the present invention is to provide a kind of tumor antigen protein matter and tumor antigen peptide that can be used for liver cancer and lung cancer therapy.
The objective of the invention is to realize by the following technical solutions:
The invention provides a kind of tumor antigen protein matter, this protein is by decomposing in the cell, can produce the peptide fragment combine with major histocompatibility complex (MHC)-I quasi-molecule, can be discerned by the T cell at bonding state, it has following (a) or (b) described aminoacid sequence:
(a) has the aminoacid sequence shown in the sequence 1;
(b) with the replacement of the aminoacid sequence in (a) through one or several amino-acid residue, disappearance or interpolation are prominent
Become the derived protein produced, and this derived protein has identical functions with (a) protein.
The invention provides a kind of dna sequence dna, its described tumor antigen protein matter of encoding.
Dna sequence dna of the present invention has the nucleotide sequence shown in the sequence 2, and its accession number in gene library is: TPTE AF007118.
The invention provides of the application of described protein as tumor-testis antigen.
The invention provides of the application of described gene as the tumor-testis antigen gene.
The invention provides the tumor antigen peptide of the peptide segment same function that a kind of and described tumor antigen protein matter produced, it has the 9th～the 17th, the 95th～the 102nd, the 100th～the 108th, the 102nd～the 110th, the 130th～the 138th, the 137th～the 145th, the 195th～the 203rd, the 235th～the 244th, the 263rd～the 272nd, the 277th～the 287th, the 308th～the 319th, the 330th～the 338th or the 523rd～the 535th aminoacid sequence of aminoacid sequence in the sequence 1 respectively.
The application of tumor antigen protein matter of the present invention in preparation treatment liver-cancer medicine.
The application of tumor antigen protein matter of the present invention in preparation treatment lung-cancer medicament.
The application of tumor antigen peptide of the present invention in preparation treatment liver-cancer medicine.
The application of tumor antigen peptide of the present invention in preparation treatment liver-cancer medicine.
The advantage of tumor antigen protein matter provided by the invention and tumor antigen peptide is: the present invention is the tumor-testis antigen gene with the TPTE gene identification first; When using immunization method treatment cancer, can produce a immune response with these antigen induction bodies at tumour cell, thereby do not killing and wounding the Normocellular while the intravital tumour cell of specific killing and reach the effect that treatment or control tumour cell shift; Simultaneously, can be by to this tumor antigen gene or detection of antibodies, to generation, the development of tumour and whether have to shift and diagnose.
Description of drawings
Fig. 1 is the RT-PCR detected result of the gene TPTE of code book invention antigen protein 16 kinds of adult's healthy tissuess; Among the figure 1～16 represents adult's healthy tissues spleen, prostate gland, ovary, small intestine, large intestine, white corpuscle, testis, heart, lung, liver, brain, kidney, placenta, skeletal muscle, pancreas, thymus gland respectively;
Fig. 2 is that the gene TPTE of code book invention antigen protein is the cancerous tissue of liver cancer and the RT-PCR result of paired cancer beside organism; Ca among the figure represents cancerous tissue, and adj represents paired cancer beside organism;
Fig. 3 is the Northern blot result of the gene TPTE of code book invention antigen protein in liver cancer tissue and paired cancer beside organism; Ca among the figure represents cancerous tissue, and adj represents paired cancer beside organism;
Fig. 4 is the recombinant protein of antigen protein of the present invention in intestinal bacteria and the representative result of hepatocarcinoma patient sero-reaction that detects by the Westernblot method; M among the figure represents the protein molecular weight standard reference, sf9 insect cell lysate that the tumor-testis antigen recombinant protein among the present invention is arranged and the result who resists histidine-tagged monoclonal antibody reactive are expressed in 1 representative, 2 represent the result of tumor-testis antigen recombinant protein and anti-histidine-tagged monoclonal antibody reactive among the present invention of purifying, 3 representatives are expressed the sf9 insect cell lysate of the tumor-testis antigen recombinant protein among the present invention and the result of hepatocarcinoma patient sero-reaction, 4 represent the tumor-testis antigen recombinant protein among the present invention of purifying and the result of hepatocarcinoma patient sero-reaction, on behalf of transfection, 5 the st9 insect cell lysate of empty expression vector and the result of hepatocarcinoma patient sero-reaction are arranged, and on behalf of transfection, 6 the sf9 insect cell lysate of irrelevant albumen contrast expression vector and the result of hepatocarcinoma patient sero-reaction are arranged;
Fig. 5 is the recombinant protein of tumor-testis antigen protein of the present invention in the sf9 insect cell and the result of hepatocarcinoma patient sero-reaction who detects by the ELISA method; Wherein X-axis is represented the extent of dilution of serum, the absorbancy when on behalf of wavelength, Y-axis be 410nm; "-●-" " ▲-" " ◆-" " ■-" "---" " ■-" represent the result of recombinant protein and 6 different tumour patient sero-reactions respectively.
Embodiment
The screening of embodiment 1, TPTE gene
Be expressed as descriptor with testes specificity and in the gene database (GenBank) of American National biotechnology information center website (http://www.ncbi.nlm.nih.gov) and literature search database (PubMed), retrieve the gene of testis specific expression in people's healthy tissues that those have had strict difinition, but it must be up to the present without any the report relevant with tumour.We have obtained to comprise the gene of several testis specific expressions in people's healthy tissues of TPTE gene thus, their target gene as our next step Unigene and SAGE database analysis.
Unigene is a network tool that all Genbank sequences that will derive from same gene are sorted out automatically.In the Unigene database, each Unigene gene include derive from various tissues but belong to the sequence that the segment of same gene varies in size, the tissue-derived and expressing information of these sequences is all indicated.SAGE (serial analysis of genetic expression) database is one can carry out the express spectra of a certain specific gene quantitatively and online tool qualitatively.Therefore, application Unigene and SAGE database just can be analyzed the time and space expression of a certain special genes, thereby obtain its correlation function information.In process of the present invention, three standards are used to screen candidate gene, obtain tumor-testis (CT) antigen gene of purpose with expectation: 1. candidate gene must be the gene of testis specific expression in people's healthy tissues of strict difinition, but it must be up to the present without any the report relevant with tumour.2. in the Unigene database analysis in process of the present invention, must contain the expressed sequence tag (EST) 3. in the SAGE database analysis in process of the present invention that derives from tumour in the Unigene data of candidate gene, if there is the SAGE label in candidate gene, have only the SAGE label of strict corresponding candidate gene just can be applied in the analysis of candidate gene.After above-mentioned three standards were used, candidate gene TPTE was considered to most possible tumor-testis antigen gene.In the Unigene of TPTE gene data, have 47 EST fragments, though 43 EST wherein derive from testis tissue, other 4 is to derive from tumor tissues; In the SAGE of TPTE gene data, the TPTE gene has 2 SAGE labels that derive from tumor tissues.Based on above-mentioned analysis, think that the TPTE gene might be goal gene-tumor-testis antigen gene that desire is sought among the present invention, next step is proved contrived experiment.
CDNA (the spleen of 16 kinds of commercial people's healthy tissuess of the CLONTECH of biotech company, prostate gland, testis, ovary, small intestine, large intestine, white corpuscle, heart, lung, liver, brain, kidney, pancreas, placenta, skeletal muscle, thymus gland), derive from the cancerous tissue of 62 routine hepatocarcinoma patients and the cDNA of paired cancer beside organism, derive from the cancerous tissue of 14 routine lung cancer patients and the cDNA of paired cancer beside organism, the cDNA that derives from the cancerous tissue of 14 routine Patients with Gastric Cancer and paired cancer beside organism with derive from the cancerous tissue of 14 routine lung cancer patients and the cDNA of paired cancer beside organism is used to detect the expression of TPTE gene at healthy tissues and tumor tissues.
Carry out the condition of RT-PCR among the present invention: use the advanced warm start archaeal dna polymerase of CLONTECH company, 94 ℃, 15 seconds; 65 ℃, 30 seconds; 72 ℃, 90 seconds, 30 circulations, afterwards, 72 ℃, 6 minutes.Carry out the primer sequence of RT-PCR, forward primer: cca caa tgg tcc acc cac aaa tg; Reverse primer: aac atg tgg cagggt tgg aaa gaa c.Found that: the TPTE gene is expressed in 40% liver cancer sample, 36% lung cancer, and (as Fig. 2) do not express in paired cancer beside organism with it; In 16 kinds of important healthy tissuess of adult, discovery TPTE gene is only expressed in testis tissue among the present invention, and the expression amount of TPTE gene in liver cancer is consistent with the expression amount at testis, and lower than testis in lung cancer.Based on above experimental data, proof is consistent with Unigene and SAGE database analysis result among the embodiment 1 in the present embodiment, and the TPTE gene is a new tumor-testis antigen gene.
Embodiment 4, analyze the expression of TPTE gene in liver cancer and lung cancer with the method for Northern hybridization
From the cancerous tissue of liver cancer and lung cancer patient and paired cancer beside organism, extract total RNA with TRIZOL reagent (PROMEGA), then use mRNA separating kit (PROMEGA) separating mRNA from total RNA.Under the condition that methane amide, formaldehyde exist,, carry out forwarding on the Hybond-N+ nylon membrane (Amersham) after the agarose electrophoresis, fix with UV-crosslinked method with the mRNA sex change of 2ug.With the dna fragmentation of coming out that increases among digoxin dna probe labelling kit (Roche) the mark embodiment 2, to make dna probe, hybridize according to the Northern hybridizing method of routine and the mRNA on the film, carry out radioautograph afterwards, detect the mRNA of the Testiculo-tumor antigen protein plasmagene TPTE among the present invention.Then, in 1%SDS solution, boil detecting the used film of this gene mRNA, remove the probe of digoxigenin labeled after, make probe with the house-keeping gene G3PDH of mark, use the same method and carry out Northern hybridization, detected mRNA makes positive control.The result as shown in Figure 3.From this result as can be seen, the mRNA of tumor antigen protein plasmagene of the present invention only expresses in cancerous tissue, and paired cancer beside organism does not express.Consistent with the characteristic of tumor-testis antigen gene.
Use Bac-To-Bac baculovirus expression system (GIBCOBRL), in the sf9 insect cell, under 27 ℃ of growth conditionss, express recombinant protein matter.The SDS-PAGE protein electrophoresis is identified Recombinant Protein Expression.Afterwards, application of nickel ion affinity chromatography pillar (INVOTRIGEN) with recombinant protein from sf9 insect cell whole protein, separate, purifying comes out.The monoclonal antibody of 6 Histidines that have with anti-recombinant protein by the Weatem hybridizing method, is identified recombinant protein.The baculovirus storage liquid of expressing tumor-testis antigen TPTE and the coli strain DH10Bac that contains plasmid pFASTBac-TPTE are stored in-80 ℃ of cryogenic refrigerators that the immunity of Department Of Medicine, Peking University's preclinical medicine institute of the People's Republic of China (PRC) is T cell research chamber, and date saved is on July 12nd, 2002.
With reference to The Journal of Experimental Medicine, 187:1349, the method in 1998, the serum of screening TPTE mRNA transcript male tumour patient finds to exist the antibody (Fig. 4,5) of anti-TPTE recombinant protein in the serum of tumour patient.Therefore, TPTE is a new tumor-testis antigen, has the induced tumor patient and produces immunne response, repels the ability of killing tumor cell, and the potential of the clinical immunotherapy of the tumour of being applied to is arranged.
Formation and the CTL killing experiments in vitro of embodiment 7, the external evoked CTL of application tumor antigen peptide
With reference to the experimental technique in the Chinese general surgery magazine (17:218,2002).PBMC (peripheral blood lymphocytes) 2ml of 2 * 106/ml concentration is incubated in 24 well culture plates, and the action effect lymphocyte simultaneously, presses 2 * 10 with other a part of PBMC
6/ ml concentration dilution adds the tumor antigen peptide 40ug/ml with aminoacid sequence of the 9th～the 17th in the sequence 1 in the RPMI1640 substratum, 37 ℃ hatch 2 hours after, through 30GY
60The Co gammairradiation, centrifugal, flush away residue peptide, be used as antigen deduction cell, it by effector cell: APC 1.3: 1 APC cell count, the antigen cell of deducting a percentage is added above-mentioned effector cell's co-cultivation, after 24 hours, add IL-2 (Australian Ludwig Institute for Cancer Research provides) 25U/ml and continue to cultivate.Later on every 7 days, by the effector cell: antigen deduction cell was that 1.3: 1 antigen deduction cell quantity adds the antigen cell of deducting a percentage among the effector cell and stimulates 3 times again, detected the lethal effect of CTL in the 28th day.Killing experiments is undertaken by following: (1) adopts the on-radiation cell toxicant to analyze box, measures CTL and target cell and cultivates the lethal effect that back LDH releasing value detects CTL altogether.Operate according to the test kit recommended program.Used substratum is the no phenol red RPMI1640 that contains 3%FCS, and 3 multiple holes are all established in every kind of reaction, measures the spontaneous releasing value of target cell, the maximum releasing value of target cell, the spontaneous releasing value of effector cell, volume correction value and substratum background value simultaneously.Use following formula and calculate lethal effect: lethal effect (%)=(the spontaneous releasing value of the spontaneous releasing value-target cell of experimental value-effector cell)/(the spontaneous releasing value of the maximum releasing value-target cell of target cell) * 100.(2) after mixed lymphocytes and target cell are cultivated 4 hours altogether, observe the morphological change of lymphocyte and target cell.After 28 days, peripheral blood lymphocytes has increased 32 times, the ratio of CD3 positive cell 16% (from 54% to 70%) that risen wherein, CTL ratio 20% (from 36% to 56%) that risen.As the effector cell: when target cell is 10: 1, CTL to tumor antigen peptide (biochemical company limited is synthetic by the Shanghai gill) hatch be 62.5% from the lymphoblastic lethal effect of body, lethal effect to tumour antigen TPTE male tumour cell is 40.2%, and both are all apparently higher than to the lethal effect (1.6%) from the tumour cell of lymphoblastic lethal effect of body (17.9%) and tumour antigen TPTE feminine gender; As the effector cell: when target cell is 3.3: 1, CTL to tumor antigen peptide hatch be 53.6% from the lymphoblastic lethal effect of body, apparently higher than to from the lymphoblastic lethal effect of body (15.6%).The tumour antigen Toplink of these presentation of results tumour antigens TPTE effectively induces the CTL with specific killing tumour cell from the PBMC of tumour patient, thereby strengthens the ability that tumour patient is removed tumour.
Use in the sequence 1 other tumor antigen peptide of the 95th～the 102nd, the 100th～the 108th, the 102nd～the 110th, the 130th～the 138th, the 137th～the 145th, the 195th～the 203rd, the 235th～the 244th, the 263rd～the 272nd, the 277th～the 287th, the 308th～the 319th, the 330th～the 338th or the 523rd～the 535th amino acids sequence to carry out same experiment, obtain same result.
Embodiment 8, CTL cell are stimulated the detection of back secretion IFN γ ability by tumor antigen peptide
With reference to the experimental technique in the Chinese Medical Journal (81:1234,2001).Carry out the quantitative of IFN-γ with enzyme linked immunological spot detection method (ELISPOT).The flat nitrocellulose plate in 96 holes (available from French Millipore company), with anti-people IFN γ monoclonal antibody (be dissolved in the pH9.6 carbonate buffer solution, final concentration is 2ug/ml) bag quilt, 4 ℃ are spent the night; After phosphate buffered saline buffer (PBS) washing through containing 0.05%Tween20 in the 2nd day, with the RPMI1640 nutrient solution room temperature lucifuge sealing that contains 10%AB serum 1 hour, with the 0.05%TweenPBS washing, add again through 7 days inductive effector cells (effector cells, E) 5 * 10
4Individual/hole.After this experiment divides two groups to be carried out, and promptly effector cell and T2 groups of cells (E+T2), effector cell and T2 cell load tumor antigen peptide group (E+T2 tumor antigen peptide), does two multiple holes for every group.Simple T2 cell and the T2 cell that loaded the 10ug/ml tumor antigen peptide in serum-free RPMI1640,37 ℃, 5%CO
2Hatched warp under the condition 2 hours
60Co gamma-rays 100GY irradiation, with after the unnecessary antigen peptide of serum-free RPMI1640 flush away as irritation cell, with 1 * 10
5Individual/hole adds each effector cell hole; This reaction system in the RPMI1640 nutrient solution of not factor-containing and serum, 37 ℃, 5%CO
2After hatching 18～20h under the condition, fully wash culture plate to remove residual cell with 0.05%TweenPBS; It is anti-to add the biotin labeled anti-people IFN γ of 0.2ug/ml two subsequently, hatches 2 hours in 37 ℃, washes plate; The Streptavidin 1ug/m that adds alkali phosphatase enzyme mark again, lucifuge was hatched 1 hour under the room temperature; Wash plate, add substrate colour developing liquid, lucifuge colour developing 5 minutes is with tap water flushing, termination reaction.After the question response plate dries, count every hole spot number of purple darkly down, obtain the mean value in two multiple holes in dissecting microscope.E+T2 tumor antigen peptide group spot number deducts E+T2 group spot number and is the special CTL cell frequency of tumour antigen.During ELISPOT detects, to produce the CD8 of IFN γ
+The frequency of T cell is an index, measures the respondent to tumour antigen TPTE respectively in the patient of expression of tumor tissue TPTE mRNA, does not all detect corresponding specific immune among the patient that TPTEmRNA expresses and replys and have at cancerous tissue.At part cancer tissues expressed TPTEmRNA, but serum do not have in the tumour patient of TPTE antibody, still can detect the immunne response of CD8+T cell to tumour antigen TPTE and antigen peptide.This experiment provides foundation for experiment in the clinical body of further using tumour antigen TPTE and antigen peptide treatment tumour.
The preparation of the tumor antigen protein matter of embodiment 9, sudden change and serum antibody screening thereof
Use the DNA that well-known method has prepared following random mutation, the 413rd base in the sequence number 2 sported C by T, also just the 138th amino acid in the sequence number 1 is sported P by L thus; The 38th base in the sequence number 2 sported C by T, also just the 38th amino acid in the sequence number 1 is sported A by V thus.The dna clone of sudden change in expression vector, is expressed the tumour antigen of sudden change, in detail with reference to embodiment 4.Use the serum of the tumour antigen of the sudden change for preparing, find in the serum of tumour patient, also to exist the antibody of these sudden change tumour antigens with reference to embodiment 5 screening tumour patients.Because the mutational site among this embodiment is selected at random, also there is the antibody of the tumor antigen protein matter that produces at other site mutation in this explanation in the serum of tumour patient.This embodiment illustrates that the tumour antigen of sudden change also has the induced tumor patient to produce immunne response, repels the ability of killing tumor cell, and the potential of the clinical immunotherapy of the tumour of being applied to is arranged.
Use tumor antigen protein matter of the present invention and tumor antigen peptide the medicine of activation antineoplastic immune can be provided, diagnostic method of tumors can be provided.The tumor antigen protein matter among anti-the present invention or the antibody of tumor antigen peptide can be used for the preparation of affinity chromatography, cDNA library screening, immunology diagnosis or medicine.
Sequence table comprises sequence 1 and sequence 2
Sequence length: 551
Topology: linearity
Sequence kind: peptide
The source:
Biological name: people (Homo sapiens)
Tissue types: liver cancer tissue
Sequence signature:
The mark of feature: peptide
Location: 1..551
Sequence 1:
Met?Aan?Glu?Ser?Pro?Asp?Pro?Thr?Asp?Leu?Ala?Gly?Val?Ile?Ile?Glu
1 5 10 15
Leu?Gly?Pro?Asn?Asp?Ser?Pro?Gln?Thr?Ser?Glu?Phe?Lys?Gly?Ala?Thr
20 25 30
Glu?Glu?Ala?Pro?Ala?Lys?Glu?Ser?Pro?His?Thr?Ser?Glu?Phe?Lys?Gly
35 40 45
Ala?Ala?Arg?Val?Ser?Pro?Ile?Ser?Glu?Ser?Val?Leu?Ala?Arg?Leu?Ser
50 55 60
Lys?Phe?Glu?Val?Glu?Asp?Ala?Glu?Asn?Val?Ala?Ser?Tyr?Asp?Ser?Lys
65 70 75 80
Ile?Lys?Lys?Ile?Val?His?Ser?Ile?Val?Ser?Ser?Phe?Ala?Phe?Gly?Leu
85 90 95
Phe?Gly?Val?Phe?Leu?Val?Leu?Leu?Asp?Val?Thr?Leu?Ile?Leu?Ala?Asp
100 105 110
Leu?Ile?Phe?Thr?Asp?Ser?Lys?Leu?Tyr?Ile?Pro?Leu?Glu?Tyr?Arg?Ser
115 120 125
Ile?Ser?Leu?Ala?Ile?Ala?Leu?Phe?Phe?Leu?Met?Asp?Val?Leu?Leu?Arg
130 135 140
Val?Phe?Val?Glu?Arg?Arg?Gln?Gln?Tyr?Phe?Ser?Asp?Leu?Phe?Asn?He
145 150 155 160
Leu?Asp?Thr?Ala?Ile?Ile?Val?Ile?Leu?Leu?Leu?Val?Asp?Val?Val?Tyr
165 170 175
Ile?Phe?Phe?Asp?Ile?Lys?Leu?Leu?Arg?Asn?Ile?Pro?Arg?Trp?Thr?His
180 185 190
Leu?Leu?Arg?Leu?Leu?Arg?Leu?Ile?Ile?Leu?Leu?Arg?Ile?Phe?His?Leu
195 200 205
Phe?His?Gln?Lys?Arg?Gln?Leu?Glu?Lys?Leu?Ile?Arg?Arg?Arg?Val?Ser
210 215 220
Glu?Asn?Lys?Arg?Arg?Tyr?Thr?Arg?Asp?Gly?Phe?Asp?Leu?Asp?Leu?Thr
225 230 235 240
Tyr?Val?Thr?Glu?Arg?Ile?Ile?Ala?Met?Ser?Phe?Pro?Ser?Ser?Gly?Arg
245 250 255
Gln?Ser?Phe?Tyr?Arg?Asn?Pro?Ile?Lys?Glu?Val?Val?Arg?Phe?Leu?Asp
260 265 270
Lys?Lys?His?Arg?Asn?His?Tyr?Arg?Val?Tyr?Asn?Leu?Cys?Ser?Glu?Arg
275 280 285
Ala?Tyr?Asp?Pro?Lys?His?Phe?His?Asn?Arg?Val?Val?Arg?Ile?Met?Ile
290 295 300
Asp?Asp?His?Asn?Val?Pro?Thr?Leu?His?Gln?Met?Val?Val?Phe?Thr?Lys
305 310 315 320
Glu?Val?Asn?Glu?Trp?Met?Ala?Gln?Asp?Leu?Glu?Asn?Ile?Val?Ala?Ile
325 330 335
His?Cys?Lys?Gly?Gly?Thr?Asp?Arg?Thr?Gly?Thr?Met?Val?Cys?Ala?Phe
340 345 350
Leu?Ile?Ala?Ser?Glu?Ile?Cys?Ser?Thr?Ala?Lys?Glu?Ser?Leu?Tyr?Tyr
355 360 365
Phe?Gly?Glu?Arg?Arg?Thr?Asp?Lys?Thr?His?Ser?Glu?Lys?Phe?Gln?Gly
370 375 380
Val?Glu?Thr?Pro?Ser?Gln?Lys?Arg?Tyr?Val?Ala?Tyr?Phe?Ala?Gln?Val
385 390 395 400
Lys?His?Leu?Tyr?Asn?Trp?Asn?Leu?Pro?Pro?Arg?Arg?Ile?Leu?Phe?Ile
405 410 415
Lys?His?Phe?Ile?Ile?Tyr?Ser?Ile?Pro?Arg?Tyr?Val?Arg?Asp?Leu?Lys
420 425 430
Ile?Gln?Ile?Glu?Met?Glu?Lys?Lys?Val?Val?Phe?Ser?Thr?Ile?Ser?Leu
435 440 445
Gly?Lys?Cys?Ser?Val?Leu?Asp?Asn?Ile?Thr?Thr?Asp?Lys?Ile?Leu?Ile
450 455 460
Asp?Val?Phe?Asp?Gly?Pro?Pro?Leu?Tyr?Asp?Asp?Val?Lys?Val?Gln?Phe
465 470 475 480
Phe?Tyr?Ser?Asn?Leu?Pro?Thr?Tyr?Tyr?Asp?Asn?Cys?Ser?Phe?Tyr?Phe
485 490 495
Trp?Leu?His?Thr?Ser?Phe?Ile?Glu?Asn?Asn?Arg?Leu?Tyr?Leu?Pro?Lys
500 505 510
Asn?Glu?Leu?Asp?Asn?Leu?His?Lys?Gln?Lys?Ala?Arg?Arg?Ile?Tyr?Pro
515 520 525
Ser?Asp?Phe?Ala?Val?Glu?Ile?Leu?Phe?Gly?Glu?Lys?Met?Thr?Ser?Ser
530 535 540
Asp?Val?Val?Ala?Gly?Ser?Asp
545 550
Sequence length: 2168
Chain: two strands
Topology: linearity
Sequence kind: cDNA to mRNA
Hypothetical sequence: do not have
Antisense: do not have
Origin:
Biological name: people (Homo sapiens)
Tissue types: liver cancer tissue
Sequence signature:
The expression mark of feature: 5 ' UTR
Location: 1..339
The expression mark of feature: CDS
Location: 340.1995
The expression mark of feature: 3 ' UTR
Location: 1996..2153
The expression mark of feature: polyA site
Location: 2154..2168
Sequence 2:
GAATCCGCGG?GGAGGGCACA?ACAGCTGCTA?CCTGAACAGT?TTCTGACCCA?ACAGTTACCC 60
AGCGCCGGAC?TCGCTGCGCC?CCGGCGGCTC?TAGGGACCCC?CGGCGCCTAC?ACTTAGCTCC 120
GCGCCCGAGA?GAATGTTGGA?CCGACGACAC?AAGACCTCAG?ACTTGTGTTA?TTCTAGCAGC 180
TGAACACACC?CCAGGCTCTT?CTGACCGGCA?GTGGCTCTGG?AAGCAGTCTG?GTGTATAGAG 240
TTATGGATTC?ACTACCAGAT?TCTACTGTAT?GCTCTTGACA?ACTATGACCA?CAATGGTCCA 300
CCCACAAATG?AATTATCAGG?AGTGAACCCA?GAGGCACGTA?TGAATGAAAG?TCCTGATCCG 360
ACTGACCTGG?CGGGAGTCAT?CATTGAGCTC?GGCCCCAATG?ACAGTCCACA?GACAAGTGAA 420
TTTAAAGGAG?CAACCGAGGA?GGCACCTGCG?AAAGAAAGCC?CACACACAAG?TGAATTTAAA 480
GGAGCAGCCC?GGGTGTCACC?TATCAGTGAA?AGTGTGTTAG?CACGACTTTC?CAAGTTTGAA 540
GTTGAAGATG?CTGAAAATGT?TGCTTCATAT?GACAGCAAGA?TTAAGAAAAT?TGTGCATTCA 600
ATTGTATCAT?CCTTTGCATT?TGGACTATTT?GGAGTTTTCC?TGGTCTTACT?GGATGTCACT 660
CTCATCCTTG?CCGACCTAAT?TTTCACTGAC?AGCAAACTTT?ATATTCCTTT?GGAGTATCGT 720
TCTATTTCTC?TAGCTATTGC?CTTATTTTTT?CTCATGGATG?TTCTTCTTCG?AGTATTTGTA 780
GAAAGGAGAC?AGCAGTATTT?TTCTGACTTA?TTTAACATTT?TAGATACTGC?CATTATTGTG 840
ATTCTTCTGC?TGGTTGATGT?CGTTTACATT?TTTTTTGACA?TTAAGTTGCT?TAGGAATATT 900
CCCAGATGGA?CACATTTACT?TCGACTTCTA?CGACTTATTA?TTCTGTTAAG?AATTTTTCAT 960
CTGTTTCATC?AAAAAAGACA?ACTTGAAAAG?CTGATAAGAA?GGCGGGTTTC?AGAAAACAAA 1020
AGGCGATACA?CAAGGGATGG?ATTTGACCTA?GACCTCACTT?ACGTTACAGA?ACGTATTATT 1080
GCTATGTCAT?TTCCATCTTC?TGGAAGGCAG?TCTTTCTATA?GAAATCCAAT?CAAGGAAGTT 1140
GTGCGGTTTC?TAGATAAGAA?ACACCGAAAC?CACTATCGAG?TCTACAATCT?ATGCAGTGAA 1200
AGAGCTTACG?ATCCTAAGCA?CTTCCATAAT?AGGGTCGTTA?GAATCATGAT?TGATGATCAT 1260
AATGTCCCCA?CTCTACATCA?GATGGTGGTT?TTCACCAAGG?AAGTAAATGA?GTGGATGGCT 1320
CAAGATCTTG?AAAACATCGT?AGCGATTCAC?TGTAAAGGAG?GCACAGATAG?AACAGGAACT 1380
ATGGTTTGTG?CCTTCCTTAT?TGCCTCTGAA?ATATGTTCAA?CTGCAAAGGA?AAGCCTGTAT 1440
TATTTTGGAG?AAAGGCGAAC?AGATAAAACC?CACAGCGAAA?AATTTCAGGG?AGTAGAAACT 1500
CCTTCTCAGA?AGAGATATGT?TGCATATTTT?GCACAAGTGA?AACATCTCTA?CAACTGGAAT 1560
CTCCCTCCAA?GACGGATACT?CTTTATAAAA?CACTTCATTA?TTTATTCGAT?TCCTCGTTAT 1620
GTACGTGATC?TAAAAATCCA?AATAGAAATG?GAGAAAAAGG?TTGTCTTTTC?CACTATTTCA 1680
TTAGGAAAAT?GTTCGGTACT?TGATAACATT?ACAACAGACA?AAATATTAAT?TGATGTATTC 1740
GACGGTCCAC?CTCTGTATGA?TGATGTGAAA?GTGCAGTTTT?TCTATTCGAA?TCTTCCTACA 1800
TACTATGACA?ATTGCTCATT?TTACTTCTGG?TTGCACACAT?CTTTTATTGA?AAATAACAGG 1860
CTTTATCTAC?CAAAAAATGA?ATTGGATAAT?CTACATAAAC?AAAAAGCACG?GAGAATTTAT 1920
CCATCAGATT?TTGCCGTGGA?GATACTTTTT?GGCGAGAAAA?TGACTTCCAG?TGATGTTGTA 1980
GCTGGATCCG?ATTAAGTATA?GCTCCCCCTT?CCCCTTCTGG?GAAAGAATTA?TGTTCTTTCC 2040
AACCCTGCCA?CATGTTCATA?TATCCTAAAT?CTATCCTAAA?TGTTCCCTTG?AAGTATTTAT 2100
TTATGTTTAT?ATATGTTTAT?ACATGTTCTT?CAATAAATCT?ATTACATATA?TATAAAAAAA 2160
AAAAAAAA 2168
SEQUENCE?LISTING
＜110〉Peking University
＜120〉a kind of tumor antigen protein matter and tumor antigen peptide
<130>PI034448
<160>2
<170>PatentIn?version3.1
<210>1
<211>551
<212>PRT
<213>Homo?sapiens
<400>1
Met?Asn?Glu?Ser?Pro?Asp?Pro?Thr?Asp?Leu?Ala?Gly?Val?Ile?Ile?Glu
1 5 10 15
Leu?Gly?Pro?Asn?Asp?Ser?Pro?Gln?Thr?Ser?Glu?Phe?Lys?Gly?Ala?Thr
20 25 30
Glu?Glu?Ala?Pro?Ala?Lys?Glu?Ser?Pro?His?Thr?Ser?Glu?Phe?Lys?Gly
35 40 45
Ala?Ala?Arg?Val?Ser?Pro?Ile?Ser?Glu?Ser?Val?Leu?Ala?Arg?Leu?Ser
50 55 60
Lys?Phe?Glu?Val?Glu?Asp?Ala?Glu?Asn?Val?Ala?Ser?Tyr?Asp?Ser?Lys
65 70 75 80
Ile?Lys?Lys?Ile?Val?His?Ser?Ile?Val?Ser?Ser?Phe?Ala?Phe?Gly?Leu
85 90 95
Phe?Gly?Val?Phe?Leu?Val?Leu?Leu?Asp?Val?Thr?Leu?Ile?Leu?Ala?Asp
100 105 110
Leu?Ile?Phe?Thr?Asp?Ser?Lys?Leu?Tyr?Ile?Pro?Leu?Glu?Tyr?Arg?Ser
115 120 125
Ile?Ser?Leu?Ala?Ile?Ala?Leu?Phe?Phe?Leu?Met?Asp?Val?Leu?Leu?Arg
130 135 140
Val?Phe?Val?Glu?Arg?Arg?Gln?Gln?Tyr?Phe?Ser?Asp?Leu?Phe?Asn?Ile
145 150 155 160
Leu?Asp?Thr?Ala?Ile?Ile?Val?Ile?Leu?Leu?Leu?Val?Asp?Val?Val?Tyr
165 170 175
Ile?Phe?Phe?Asp?Ile?Lys?Leu?Leu?Arg?Asn?Ile?Pro?Arg?Trp?Thr?His
180 185 190
Leu?Leu?Arg?Leu?Leu?Arg?Leu?Ile?Ile?Leu?Leu?Arg?Ile?Phe?His?Leu
195 200 205
Phe?His?Gln?Lys?Arg?Gln?Leu?Glu?Lys?Leu?Ile?Arg?Arg?Arg?Val?Ser
210 215 220
Glu?Asn?Lys?Arg?Arg?Tyr?Thr?Arg?Asp?Gly?Phe?Asp?Leu?Asp?Leu?Thr
225 230 235 240
Tyr?Val?Thr?Glu?Arg?Ile?Ile?Ala?Met?Ser?Phe?Pro?Ser?Ser?Gly?Arg
245 250 255
Gln?Ser?Phe?Tyr?Arg?Asn?Pro?Ile?Lys?Glu?Val?Val?Arg?Phe?Leu?Asp
260 265 270
Lys?Lys?His?Arg?Asn?His?Tyr?Arg?Val?Tyr?Asn?Leu?Cys?Ser?Glu?Arg
275 280 285
Ala?Tyr?Asp?Pro?Lys?His?Phe?His?Asn?Arg?Val?Val?Arg?Ile?Met?Ile
290 295 300
Asp?Asp?His?Asn?Val?Pro?Thr?Leu?His?Gln?Met?Val?Val?Phe?Thr?Lys
305 310 315 320
Glu?Val?Asn?Glu?Trp?Met?Ala?Gln?Asp?Leu?Glu?Asn?Ile?Val?Ala?Ile
325 330 335
His?Cys?Lys?Gly?Gly?Thr?Asp?Arg?Thr?Gly?Thr?Met?Val?Cys?Ala?Phe
340 345 350
Leu?I1e?Ala?Ser?Glu?Ile?Cys?Ser?Thr?Ala?Lys?Glu?Ser?Leu?Tyr?Tyr
355 360 365
Phe?Gly?Glu?Arg?Arg?Thr?Asp?Lys?Thr?His?Ser?Glu?Lys?Phe?Gln?Gly
370 375 380
Val?Glu?Thr?Pro?Ser?Gln?Lys?Arg?Tyr?Val?Ala?Tyr?Phe?Ala?Gln?Val
385 390 395 400
Lys?His?Leu?Tyr?Asn?Trp?Asn?Leu?Pro?Pro?Arg?Arg?Ile?Leu?Phe?Ile
405 410 415
Lys?His?Phe?I1e?Ile?Tyr?Ser?Ile?Pro?Arg?Tyr?Val?Arg?Asp?Leu?Lys
420 425 430
Ile?Gln?Ile?Glu?Met?Glu?Lys?Lys?Val?Val?Phe?Ser?Thr?Ile?Ser?Leu
435 440 445
Gly?Lys?Cys?Ser?Val?Leu?Asp?Asn?Ile?Thr?Thr?Asp?Lys?Ile?Leu?Ile
450 455 460
Asp?Val?Phe?Asp?Gly?Pro?Pro?Leu?Tyr?Asp?Asp?Val?Lys?Val?Gln?Phe
465 470 475 480
Phe?Tyr?Ser?Asn?Leu?Pro?Thr?Tyr?Tyr?Asp?Asn?Cys?Ser?Phe?Tyr?Phe
485 490 495
Trp?Leu?His?Thr?Ser?Phe?Ile?Glu?Asn?Asn?Arg?Leu?Tyr?Leu?Pro?Lys
500 505 510
Asn?Glu?Leu?Asp?Asn?Leu?His?Lys?Gln?Lys?Ala?Arg?Arg?Ile?Tyr?Pro
515 520 525
Ser?Asp?Phe?Ala?Val?Glu?Ile?Leu?Phe?Gly?Glu?Lys?Met?Thr?Ser?Ser
530 535 540
Asp?Val?Val?Ala?Gly?Ser?Asp
545 550
<210>2
<211>2168
<212>DNA
<213>Homo?sapiens
<400>2
gaatccgcgg?ggagggcaca?acagctgcta?cctgaacagt?ttctgaccca?acagttaccc 60
agcgccggac?tcgctgcgcc?ccggcggctc?tagggacccc?cggcgcctac?acttagctcc 120
gcgcccgaga?gaatgttgga?ccgacgacac?aagacctcag?acttgtgtta?ttctagcagc 180
tgaacacacc?ccaggctctt?ctgaccggca?gtggctctgg?aagcagtctg?gtgtatagag 240
ttatggattc?actaccagat?tctactgtat?gctcttgaca?actatgacca?caatggtcca 300
cccacaaatg?aattatcagg?agtgaaccca?gaggcacgta?tgaatgaaag?tcctgatccg 360
actgacctgg?cgggagtcat?cattgagctc?ggccccaatg?acagtccaca?gacaagtgaa 420
tttaaaggag?caaccgagga?ggcacctgcg?aaagaaagcc?cacacacaag?tgaatttaaa 480
ggagcagccc?gggtgtcacc?tatcagtgaa?agtgtgttag?cacgactttc?caagtttgaa 540
gttgaagatg?ctgaaaatgt?tgcttcatat?gacagcaaga?ttaagaaaat?tgtgcattca 600
attgtatcat?cctttgcatt?tggactattt?ggagttttcc?tggtcttact?ggatgtcact 660
ctcatccttg?ccgacctaat?tttcactgac?agcaaacttt?atattccttt?ggagtatcgt 720
tctatttctc?tagctattgc?cttatttttt?ctcatggatg?ttcttcttcg?agtatttgta 780
gaaaggagac?agcagtattt?ttctgactta?tttaacattt?tagatactgc?cattattgtg 840
attcttctgc?tggttgatgt?cgtttacatt?ttttttgaca?ttaagttgct?taggaatatt 900
cccagatgga?cacatttact?tcgacttcta?cgacttatta?ttctgttaag?aatttttcat 960
ctgtttcatc?aaaaaagaca?acttgaaaag?ctgataagaa?ggcgggtttc?agaaaacaaa 1020
aggcgataca?caagggatgg?atttgaccta?gacctcactt?acgttacaga?acgtattatt 1080
gctatgtcat?ttccatcttc?tggaaggcag?tctttctata?gaaatccaat?caaggaagtt 1140
gtgcggtttc?tagataagaa?acaccgaaac?cactatcgag?tctacaatct?atgcagtgaa 1200
agagcttacg?atcctaagca?cttccataat?agggtcgtta?gaatcatgat?tgatgatcat 1260
aatgtcccca?ctctacatca?gatggtggtt?ttcaccaagg?aagtaaatga?gtggatggct 1320
caagatcttg?aaaacatcgt?agcgattcac?tgtaaaggag?gcacagatag?aacaggaact 1380
atggtttgtg?ccttccttat?tgcctctgaa?atatgttcaa?ctgcaaagga?aagcctgtat 1440
tattttggag?aaaggcgaac?agataaaacc?cacagcgaaa?aatttcaggg?agtagaaact 1500
ccttctcaga?agagatatgt?tgcatatttt?gcacaagtga?aacatctcta?caactggaat 1560
ctccctccaa?gacggatact?ctttataaaa?cacttcatta?tttattcgat?tcctcgttat 1620
gtacgtgatc?taaaaatcca?aatagaaatg?gagaaaaagg?ttgtcttttc?cactatttca 1680
ttaggaaaat?gttcggtact?tgataacatt?acaacagaca?aaatattaat?tgatgtattc 1740
gacggtccac?ctctgtatga?tgatgtgaaa?gtgcagtttt?tctattcgaa?tcttcctaca 1800
tactatgaca?attgctcatt?ttacttctgg?ttgcacacat?cttttattga?aaataacagg 1860
ctttatctac?caaaaaatga?attggataat?ctacataaac?aaaaagcacg?gagaatttat 1920
ccatcagatt?ttgccgtgga?gatacttttt?ggcgagaaaa?tgacttccag?tgatgttgta 1980
gctggatccg?attaagtata?gctccccctt?ccccttctgg?gaaagaatta?tgttctttcc 2040
aaccctgcca?catgttcata?tatcctaaat?ctatcctaaa?tgttcccttg?aagtatttat 2100
ttatgtttat?atatgtttat?acatgttctt?caataaatct?attacatata?tataaaaaaa 2160
aaaaaaaa 2168
Claims (5)
1, a kind of protein is as the application of tumor-testis antigen, described protein is tumor antigen protein matter, this protein is by decomposing in the cell, can produce the peptide fragment combine with major histocompatibility complex (MHC)-I quasi-molecule, can be discerned by the T cell at bonding state, it has following (a) or (b) described aminoacid sequence:
(a) has the aminoacid sequence shown in the sequence 1;
(b) with the replacement of the aminoacid sequence in (a) through one or several amino-acid residue, the derived protein that disappearance or interpolation sudden change are produced, this derived protein and protein (a) have identical functions.
2, the application of a kind of tumor antigen protein matter in preparation treatment liver-cancer medicine, described tumor antigen protein matter is by decomposing in the cell, can produce the peptide fragment combine with major histocompatibility complex (MHC)-I quasi-molecule, can be discerned by the T cell at bonding state, it has following (a) or (b) described aminoacid sequence:
(a) has the aminoacid sequence shown in the sequence 1;
(b) with the replacement of the aminoacid sequence in (a) through one or several amino-acid residue, the derived protein that disappearance or interpolation sudden change are produced, this derived protein and protein (a) have identical functions.
3, the application of a kind of tumor antigen protein matter in preparation treatment lung-cancer medicament, described tumor antigen protein matter is by decomposing in the cell, can produce the peptide fragment combine with major histocompatibility complex (MHC)-I quasi-molecule, can be discerned by the T cell at bonding state, it has following (a) or (b) described aminoacid sequence:
(a) has the aminoacid sequence shown in the sequence 1;
(b) with the replacement of the aminoacid sequence in (a) through one or several amino-acid residue, the derived protein that disappearance or interpolation sudden change are produced, this derived protein and protein (a) have identical functions.
4, a kind of application of tumor antigen peptide in preparation treatment liver-cancer medicine with the peptide fragment same function that is produced with tumor antigen protein matter, described tumor antigen protein matter is by decomposing in the cell, can produce the peptide fragment combine with major histocompatibility complex (MHC)-I quasi-molecule, can be discerned by the T cell at bonding state, it has following (a) or (b) described aminoacid sequence:
(a) has the aminoacid sequence shown in the sequence 1;
(b) with the replacement of the aminoacid sequence in (a) through one or several amino-acid residue, the derived protein that disappearance or interpolation sudden change are produced, this derived protein and protein (a) have identical functions;
Described tumor antigen peptide has the 9th～the 17th, the 95th～the 102nd, the 100th～the 108th, the 102nd～the 110th, the 130th～the 138th, the 137th～the 145th, the 195th～the 203rd, the 235th～the 244th, the 263rd～the 272nd, the 277th～the 287th, the 308th～the 319th, the 330th～the 338th or the 523rd～the 535th amino acid of aminoacid sequence shown in the sequence 1 respectively.
5, a kind of application of tumor antigen peptide in preparation treatment lung-cancer medicament with the peptide fragment same function that is produced with tumor antigen protein matter, described tumor antigen protein matter is by decomposing in the cell, can produce the peptide segment combine with major histocompatibility complex (MHC)-I quasi-molecule, can be discerned by the T cell at bonding state, it has following (a) or (b) described aminoacid sequence:
(a) has the aminoacid sequence shown in the sequence 1;
(b) with the replacement of the aminoacid sequence in (a) through one or several amino-acid residue, the derived protein that disappearance or interpolation sudden change are produced, this derived protein and protein (a) have identical functions;
Described tumor antigen peptide has the 9th～the 17th, the 95th～the 102nd, the 100th～the 108th, the 102nd～the 110th, the 130th～the 138th, the 137th～the 145th, the 195th～the 203rd, the 235th～the 244th, the 263rd～the 272nd, the 277th～the 287th, the 308th～the 319th, the 330th～the 338th or the 523rd～the 535th amino acid of aminoacid sequence shown in the sequence 1 respectively.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031360696A CN1331885C (en) | 2003-05-15 | 2003-05-15 | Tumor antigen protein and tumor antigen peptide |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031360696A CN1331885C (en) | 2003-05-15 | 2003-05-15 | Tumor antigen protein and tumor antigen peptide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1548455A CN1548455A (en) | 2004-11-24 |
| CN1331885C true CN1331885C (en) | 2007-08-15 |
Family
ID=34323211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031360696A Expired - Fee Related CN1331885C (en) | 2003-05-15 | 2003-05-15 | Tumor antigen protein and tumor antigen peptide |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1331885C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201505305D0 (en) * | 2015-03-27 | 2015-05-13 | Immatics Biotechnologies Gmbh | Novel Peptides and combination of peptides for use in immunotherapy against various tumors |
-
2003
- 2003-05-15 CN CNB031360696A patent/CN1331885C/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| A testis-specific gene,TPTE,encodes a putativetransmembrane tyrosine phosphatase and maps to thepericentromeric region of human chromosomes 21 and 13,and to chromosomes 15, 22, and Y Chen,H.,Rossier,C.,Morris,M.A.,Scott,H.S.,Gos,A.,Bairoch,A.and Antonarakis,S.E,Human Genetics,Vol.105 No.5 1999 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1548455A (en) | 2004-11-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR100306464B1 (en) | Isolated peptides that form complexes with MHC molecules HLA-C-clone 10 and uses thereof | |
| CN101384716B (en) | HLA-a*3303-restricted WT1 peptide and pharmaceutical composition comprising the same | |
| CN103149366B (en) | The method of activation of helper t cell and the composition for this method | |
| CA2411404A1 (en) | Compositions and methods for the therapy and diagnosis of ovarian cancer | |
| US20050142144A1 (en) | Epitope sequences | |
| CN101072875B (en) | Novel cancer antigen peptide and the use thereof | |
| CN101300346B (en) | Novel biological substance nesfatin and its related substances and uses thereof | |
| CA2417570C (en) | Tumor-specific t cell activation by peptide antigens | |
| JPH08507693A (en) | Nucleic acid molecule encoding a tumor rejection antigen precursor | |
| JP2003518364A (en) | Breast, gastric and prostate cancer-related antigens and uses thereof | |
| JP2002538218A (en) | New usage | |
| CN107148469A (en) | Tumor antigen peptide | |
| CN1964986A (en) | Nucleic acid molecules and proteins for the identification, assessment, prevention, and therapy of ovarian cancer | |
| CN107261111A (en) | Immune inducing agent | |
| KR20130055553A (en) | Method for identifying whether a patient will be responder or not to immunotherapy | |
| CN116970058B (en) | Tumor neoantigen polypeptide aiming at TP53 gene R249S mutation and application thereof | |
| CN102257138B (en) | Tumor antigen peptide and use thereof | |
| JP3256749B2 (en) | Tumor rejection antigen presented by HLA-B44 molecule and method of using the same | |
| CN100393745C (en) | Tumour antigen protein and tumour antigen peptide | |
| CN1331885C (en) | Tumor antigen protein and tumor antigen peptide | |
| CN1326875C (en) | Tumor antigen protein and tumor antigen peptide | |
| CN105112550A (en) | MTUSI gene serving as osterarthritis diagnosis target | |
| CN115850377A (en) | Tumor neoantigen polypeptide based on NRAS gene Q61K mutation and application thereof | |
| JP2002541803A (en) | Compositions and methods for treatment and diagnosis of breast cancer | |
| US20220265798A1 (en) | Cancer vaccine compositions and methods for using same to prevent and/or treat cancer |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070815 |