CN108715603A - A kind of Antigenic Peptide chain group for treating tumour and its application in drug - Google Patents

A kind of Antigenic Peptide chain group for treating tumour and its application in drug Download PDF

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Publication number
CN108715603A
CN108715603A CN201810584274.8A CN201810584274A CN108715603A CN 108715603 A CN108715603 A CN 108715603A CN 201810584274 A CN201810584274 A CN 201810584274A CN 108715603 A CN108715603 A CN 108715603A
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China
Prior art keywords
prt
artificial sequence
leu
artificial sequences
cell
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CN201810584274.8A
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Chinese (zh)
Inventor
刘玉强
李晓丹
霍冲
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Tianjin Hengjia Biotechnology Development Co Ltd
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Tianjin Hengjia Biotechnology Development Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/0005—Vertebrate antigens
    • A61K39/0011—Cancer antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids

Abstract

The invention discloses a kind of Antigenic Peptide chain group for the treatment of tumour individuation biological immune and its application in drug, the Antigenic Peptide chain group of the treatment tumour includes SEQ ID No：The combination of any one or at least two amino acid sequences in 1-101.The Antigenic Peptide chain group of the present invention can induce the blastomogenic Dendritic Cells of production, antigenic information thus can be presented to T cell as the Dendritic Cells of antigen presenting cell, to interact with T cell, so that T cell is generated specific killing tumour cell, play the role of killing tumor cell.

Description

A kind of Antigenic Peptide chain group for treating tumour and its application in drug
Technical field
It is the invention belongs to malignant tumour biological immune technical field of pharmaceuticals, more particularly to a kind of for tumour individuation biology The Antigenic Peptide chain group of immunization therapy and its application in drug.
Background technology
Currently, global Cancer Mortality rises increasingly, the death rate is high, poor prognosis.National Cancer Center whole nation tumour Study on prevention office exists《International journal of cancer》Largest In China scale cancer Survival data Macro or mass analysis data are issued to show, in 5 years survival rates of state's cancer are 30.9%, horizontal far below developed country；The survival rate of rural patient is only City patient's simultaneously Half.In developed country, prostate cancer, breast cancer occupy the majority, and in China, the cancers such as lung cancer, gastric cancer, liver cancer are more common, hair Sick rate and the highest cancer of the death rate are lung cancer.The traditional therapies therapeutic effect such as operation, chemotherapy, radiotherapy is limited, patient 5 years Survival rate is still relatively low；Especially eliminating side effect of radiotherapy and chemotherapy to is big, and patients ' life quality is poor, and survival rate is low.Biological immune treatment passes through machine Body immune system killing tumor cell is the new therapy of future therapeutic tumour, has been increasingly becoming the heat for the treatment of tumour Point.The more including common CIK cell immunization therapy of method of the tumour of biological immune treatment at present, DC medications treatment etc., but its Therapeutic effect is not notable, and survival is not improved significantly.It is another have stimulated with not mutated tumour high-expression albumen Immunocyte medication, research have anti tumor immune response, but due to its non-specificity expression, no doubt with the presence of side reaction, including Eye-blurred, Hearing, fash etc..
Invention content
The object of the present invention is to provide a kind of Antigenic Peptide chain group for the treatment of tumour individuation biological immune and its in medicine Application in object.
For this purpose, technical solution of the present invention is as follows：
In a first aspect, the present invention provides a kind of Antigenic Peptide chain group for treating tumour, the Antigenic Peptide chain group of the treatment tumour Including SEQ ID No：The combination of any one or at least two amino acid sequences in 1-101, such as can be SEQ ID No：Any one in 1-101, it is two arbitrary, three arbitrary, four arbitrary, it is arbitrary five until arbitrary 100 or all 101 combinations, since the limitation of length is no longer all enumerated herein.Particular sequence is as shown in table 1：
The Antigenic Peptide chain group of 1 present invention of table
Second aspect, the present invention provide a kind of pharmaceutical composition, and described pharmaceutical composition includes as described in relation to the first aspect SEQ ID No：Any one in 1-101 or at least two amino acid sequences.
Preferably, described pharmaceutical composition is aqueous suspension, solution or solid state.Preferably, the solid state is Uncoated or coated tablet form, such as pill, gel capsule, capsule or powder etc..
If described pharmaceutical composition is in drying regime, it can for example form sediment with one or more inert diluents The mixing such as powder, cellulose, sucrose, lactose or silica.It can also include in the dry state other substances, such as a kind of Or a variety of lubricants such as magnesium stearate or talcum powder, colorant, coating (sugar coated tablet) or varnish.If the drug of the present invention Composition is liquid form, then it may include containing inert diluent such as water, ethyl alcohol, glycerine, vegetable oil or atoleine Pharmaceutical solution, suspension, emulsion, syrup and elixir.Described pharmaceutical composition can also include in addition to diluent Other liquid substances, such as wetting agent, sweetener, thickener, flavoring agent or stabilizer product.
Preferably, further include the auxiliary material pharmaceutically received.Preferably, the auxiliary material is excipient, diluent, carrier, tune In taste agent, adhesive and filler any one or at least two combination, such as can be excipient, carrier and dilution Agent, the combination of flavoring agent, adhesive and filler or diluent, carrier, flavoring agent, adhesive and filler, due to length Limitation, the form of all combinations will not enumerate.
The third aspect, the Antigenic Peptide chain group that the present invention provides treatment tumour as described in relation to the first aspect are preparing treating cancer Pharmaceutical composition in application.The cancer is the cancer (i.e. entity malignant tumour) of any kind, because the present invention Antigenic Peptide chain group can induce the Dendritic Cells for generating tumour-specific, thus as the Dendritic Cells energy of antigen presenting cell Antigenic information is presented to T cell, to interact with T cell, T cell is made to generate specific killing tumour cell, to Play the role of killing tumor cell.
In the present invention, the cancer is preferably lung cancer, breast cancer, oophoroma, prostate cancer, melanoma, brain tumor, food Pipe cancer, gastric cancer, liver cancer, cancer of pancreas, colorectal cancer, kidney, cutaneum carcinoma, spongioblastoma, neuroblastoma, sarcoma, Embryonal-cell lipoma, osteochondroma, osteoma, osteosarcoma, seminoma, orchioncus, uterine cancer, H/N tumors, multiple marrow Tumor, malignant lymphoma, polycythemia vera, leukaemia, thyroid tumors, tumor of ureter, tumor of bladder, gallbladder cancer, In cholangiocarcinoma, chorioepithelioma or pediatric tumors any one or at least two combination.In addition, described pharmaceutical composition It can also be with another or at least two anti-cancer agent in conjunction applications, such as arimedex (Letrozole and/or Anastrozole) Deng.
Described pharmaceutical composition may be utilized independently or is used in combination with other drugs in given treatment, or with put Penetrate therapy or operation joint.Specifically used method is：
(1) internal stimulus method：It is 7.4PBS (Hyclone) that the Antigenic Peptide chain group of the treatment tumour, which is dissolved in pH value, In solution, concentration is adjusted to 2.5mg/ml, and covering 5%Aldara cream (iNova after 200ug are subcutaneously injected in each upper arm Pharmaceuticals Australia Pty Ltd.), once a week, 12 weeks are a cycle.
(2) stimulated in vitro method：0th day：(1) use COBE Spectra blood analysis systems (Caridian BCT, Inc. the U.S.) carry out monocyte separation acquisition filter blood volume 2500-3500ml；(2) prepare 1LDC-CM culture solutions, 500mlX2 Part；(3) cell is transferred to from 4 centrifuge tubes in 500ml centrifuge tubes, is used in combination 10mlDC-CM to rinse former centrifuge tube, and be transferred to 500ml centrifuge tubes, capping, mixing；(4) 25ml suction pipes are used, add 15mlDC-CM to each culture bottle；(5) be added IL-4 and The concentration of GM-CSF is all 1000IU/ml；(6) IL-4 is diluted, with 1%HAS to 1000IU/ml inside PBS.
6th day：The ripe mixed liquor of addition (7) dilutes IL-1 β, INF- α, IL-6 to 25ug/ml with 1%HSA-PBS；(8) eventually Concentration：IL-1β10ng/ml,INF-α10ng/ml,IL-6 15ng/ml；(9) the diluting cells factor is in 44mlDC-CM, until last Volume 50ml；(10) it inhales 1ml with aseptic straw and contains the DC-CM of cell factor to each culture bottle；(11) culture bottle is put Enter incubator (37 DEG C, 5%CO2；± 10 DEG C, ± 0.5%CO2)。
The 7-8 days：Prepare the amount that peptide chain pulse culture solution (PPM) (12) calculates the PPM needed：Culture bottle quantity X30ml+ The amount for the PPM that 300ml=needs；(13) culture bottle is taken out from incubator, bottle inner cell is transferred to 500ml sterile centrifugations Pipe；(14) culture bottle is rinsed with 30mlPPM, and flushing liquor is transferred to 500ml centrifuge tubes；(15) it is shifted with 2ml suction pipes all Supernatant is used in combination 25mlPPM that cell is resuspended, the harvest pipe DC cells of harvest and flush pipe DC cells is merged into same pipe, indicates： DC cell pipes；(16) one group of individuation specific mutations peptide chain that 1 pipe freezes is taken out, dissolves peptide chain with DC-PPM；(17) add peptide Chain to DC manage, a concentration of 5ug/ml；(18) pine lid after be put into incubator (37 DEG C, 5%CO2；± 10 DEG C, ± 0.5%CO2), often 30min takes out incubator, mixing, 1.5 hours total times；(19) the DC cells for taking 0.2ml to be resuspended, are transferred in 12X75mm pipes, Carry out endotoxin check and evaluation；(20) reduction of speed centrifuges, 1200rpm (309Xg), 7min, room temperature；(21) on being removed with 2ml suction pipes Clear liquid；(22) individuation specificity DC cells are harvested, counts and is dissolved in 1mlPBS solution；(23) tumor-draining lymphode or Injection in other.
Compared with prior art, at least provided by the present invention for the Antigenic Peptide chain group of tumour individuation biological immune treatment It has the advantages that：It is described the present invention provides a kind of Antigenic Peptide chain group for treating tumour and its application in drug The Antigenic Peptide chain group for treating tumour includes SEQ ID No：The group of any one or at least two amino acid sequences in 1-101 It closes.The Antigenic Peptide chain group of the present invention can induce the blastomogenic Dendritic Cells of production, thus as the dendron shape of antigen presenting cell Antigenic information can be presented to T cell by cell, to interact with T cell, so that T cell is generated specific killing tumour thin Born of the same parents play the role of killing tumor cell.After medication at least 6 weeks, it can obviously observe that tumour largely disappears by instrument, density Thin out, variation is apparent；Incidence of side effects is small, less to the injury of patient.
Description of the drawings
Fig. 1 is HLA*A3101-HVKITDFGR Tetramer colored graphs before and after 1 medication of embodiment；
Fig. 2 is the tumour CT scan figure before and after 1 medication of embodiment；
Fig. 3 is the tumour CT scan figure before and after 2 medication of embodiment.
Specific implementation mode
Below in conjunction with the accompanying drawings and specific embodiment the present invention is described further, but following embodiments are absolutely not to this hair It is bright to have any restrictions.
Embodiment 1
Patient A, female, 55 years old.Breast Cancer on Chest Wall shifts, multiple hepatic metastases, the clinical IV phases, vinorelbine list medicine chemotherapy 4 times After be in progress, target medicine drug resistance, take pulmonary lesions tissue biopsy, carry out full exon sequencing and HLA typing chips detection after, patient HER2 (ERBB2) 20 exon insertion mutation is carried, HLA partings are HLA-A：A*3203A*3201；HLA-B:B*3012B* 3101；HLA-C：C*0321C*0612；HLA-DQB1：DQB1*0202DQB1*1121；HLA-DRB1：DRB1*0201DRB1* 0201。
Use the specific tumor antigen peptide chain SEQ ID No of the present invention：1 treatment, 1 times a week, totally 12 weeks.Detection injection Spot detection specific C D8+Tetramer+T cells secrete situation, Yi Jitong before and after Antigenic Peptide chain group (hereinafter referred to as " medication ") The tumor size variation for spending 12 weeks before and after imaging observation medication, as a result as depicted in figs. 1 and 2.
Fig. 1 is HLA*A3101-HVKITDFGR Tetramer colored graphs, wherein Fig. 1-A are colored graph before medication, CD8 + Tetramer+T a concentration of 2.76%；Fig. 1-B are 6 weeks after stain chromatic graphs of medication, CD8+Tetramer+T a concentration of 3.72%；Figure 1-C is 12 weeks after stain chromatic graphs of medication, CD8+Tetramer+T a concentration of 6.8%；As can be seen that amount of speckle has from three group pictures Significantly raised variation tendency, illustrates that the ratio (concentration) of tumor-killing cell CD8+Tetramer+T in blood significantly improves.
Fig. 2 is the front and back right side chest metastasis CT figures of medication, and wherein Fig. 2-A scheme for CT before medication, are left hilus pulumonis tumour, compared with Big person 2cm × 5cm；Fig. 2-B are that CT schemes after medication 12 weeks, it can be seen that tumour disappears substantially, only 1 × 3cm, and front and back variation is bright It is aobvious.
Show that Antigenic Peptide chain group of the invention can induce the blastomogenic Dendritic Cells of production based on the above results, as anti- Antigenic information can be presented to T cell by original in the Dendritic Cells of delivery cell, be interacted with T cell, so that T cell is generated special Property killing tumor cell, plays the role of killing tumor cell, and with obvious effects.
Embodiment 2
Patient B, man, 70 years old, postoperative gastric cancer Lung metastases, oxaliplatin+6 week of capecitabine scheme chemotherapy, rear progress.Lung After interior transfer aspiration biopsy carries out full exon sequencing and the detection of HLA typing chips, it is aobvious that patient carries HER2 (ERBB2) 20 extra Sub- insertion mutation, HLA partings are HLA-A：A*0302A*3501；HLA-B:B*0311B*3201；HLA-C：C*0332C*0501； HLA-DQB1：DQB1*0301DQB1*0320；HLA-DRB1：DRB1*0312DRB1*1222.
Use the antigen peptide chain SEQ ID No of the treatment tumour of the present invention：2 are combined treatment, 1 times a week, totally 12 weeks.
Pretherapy and post-treatment Pulmonary artery size variation situation is as shown in figure 3, as seen from Figure 3, before medication treatment, right lung shifts Tumor size 4cm × 5cm (Fig. 3-A)；12 weeks after medication treatment, right lung metastatic tumor disappears (Fig. 3-B) substantially, and tumour is bright compared with before medication Aobvious diminution, only 2cm × 3cm, density are thin out.This example demonstrates that the Antigenic Peptide chain group of the present invention can induce the blastomogenic tree of production Antigenic information can be presented to T cell by prominent shape cell, the Dendritic Cells as antigen presenting cell, be interacted with T cell, So that T cell is generated specific killing tumour cell, plays the role of killing tumor cell, and with obvious effects.
Embodiment 3-101
Embodiment 3-101 takes variety classes, different degrees of cancer patient to carry out full exon sequencing and HLA parting cores After piece detection, patient is to carry HER2 (ERBB2) 20 exon insertion mutation patient, uses different antigen peptide chains respectively The combining form of group is treated, once a week, totally 12 weeks.HLA*A3101-HVKITDFGR of embodiment 3-101 Tetramer coloration results and pretherapy and post-treatment lung tumors size variation situation are similar with embodiment 1-2, due to the limitation of length, It is no longer repeated herein.It is thin that the Antigenic Peptide chain group of the explainable present invention of result above can induce the blastomogenic dendron shape of production Antigenic information can be presented to T cell by born of the same parents, the Dendritic Cells as antigen presenting cell, interacted with T cell, kept T thin Born of the same parents generate specific killing tumour cell, play the role of killing tumor cell, and with obvious effects.
During being treated to embodiment 1-101, with before ELISA detections antigen peptide chain, medication 3 weeks, 7 weeks, 11 weeks Specific IFN-γ secretion situation, concrete outcome is as shown in table 1.
Comparative example 1-10
To comparative example 1-10 (carry out full exon sequencing and HLA typing chips detection after, patient be carry HER2 (ERBB2) 20 exon insertion mutation patient) treat during, before detecting medication with ELISA, medication 3 weeks, 7 weeks, 11 weeks Specific IFN-γ secretion situation, concrete outcome is as shown in table 2, and dosage is identical as embodiment 1-101；Wherein, comparative example 1-5 is added without peptide chain.
From table 2 it can be seen that embodiment 1-101,11 weeks after medication, the specific IFN-γ level of T cell secretion has Significantly raised trend, illustrate to have used any one in the Antigenic Peptide chain group of the present invention or its arbitrarily combine and can increase cancer The tumor-killing ability of disease peripheral blood in patients further demonstrates the effect of the present invention.And in comparative example 1-10, IFN-γ is horizontal Also increased before and after medication, it may be possible to the effect of the nutritional ingredient of addition as a result, but all in all concentration increment it is far low In embodiment 1-101, illustrate that it does not increase the tumor-killing ability of peripheral blood in patients or the ability of blood killing tumour is far low In embodiment 1-101, the effect of the present invention is further demonstrated.
2 IFN-γ secretion of table counts list
Then, the rate of side effects of embodiment 1-101 is counted, the results are shown in Table 2, can from table 2 Go out, used the present invention Antigenic Peptide chain group after, the incidence (i.e. positive rate) of side reaction is relatively low, illustrate its side effect compared with Small, the influence and injury to patient are relatively low.
2 rate of side effects statistical result of table
It should be noted that and understanding, the feelings of the spirit and scope of the present invention required by not departing from appended claims Under condition, various modifications and improvements can be made to the present invention of foregoing detailed description.It is therefore desirable to the model of the technical solution of protection It encloses and is not limited by given any specific exemplary teachings.
Applicant states that the above content is combine specific preferred embodiment made for the present invention further specifically It is bright, and it cannot be said that specific implementation of the invention is confined to these explanations.For the ordinary skill of the technical field of the invention For personnel, without departing from the inventive concept of the premise, a number of simple deductions or replacements can also be made, all should be considered as belonging to In protection scope of the present invention.
Sequence table
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<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 47
Thr Gln Leu Met Tyr Val Met Pro Tyr Gly
1 5 10
<210> 48
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 48
Gln Leu Met Tyr Val Met Pro Tyr Gly Cys
1 5 10
<210> 49
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 49
Leu Met Tyr Val Met Pro Tyr Gly Cys Leu
1 5 10
<210> 50
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 50
Met Tyr Val Met Pro Tyr Gly Cys Leu Leu
1 5 10
<210> 51
<211> 8
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 51
Cys Leu Leu Asp His Val Gly Arg
1 5
<210> 52
<211> 8
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 52
Leu Leu Asp His Val Gly Arg Glu
1 5
<210> 53
<211> 8
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 53
Leu Asp His Val Gly Arg Glu Asn
1 5
<210> 54
<211> 8
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 54
Asp His Val Gly Arg Glu Asn Arg
1 5
<210> 55
<211> 8
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 55
His Val Gly Arg Glu Asn Arg Gly
1 5
<210> 56
<211> 8
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 56
Val Gly Arg Glu Asn Arg Gly Arg
1 5
<210> 57
<211> 9
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 57
Gly Cys Leu Leu Asp His Val Gly Arg
1 5
<210> 58
<211> 9
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 58
Cys Leu Leu Asp His Val Gly Arg Glu
1 5
<210> 59
<211> 9
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 59
Leu Leu Asp His Val Gly Arg Glu Asn
1 5
<210> 60
<211> 9
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 60
Leu Asp His Val Gly Arg Glu Asn Arg
1 5
<210> 61
<211> 9
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 61
Asp His Val Gly Arg Glu Asn Arg Gly
1 5
<210> 62
<211> 9
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 62
His Val Gly Arg Glu Asn Arg Gly Arg
1 5
<210> 63
<211> 9
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 63
Val Gly Arg Glu Asn Arg Gly Arg Leu
1 5
<210> 64
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 64
Tyr Gly Cys Leu Leu Asp His Val Gly Arg
1 5 10
<210> 65
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 65
Gly Cys Leu Leu Asp His Val Gly Arg Glu
1 5 10
<210> 66
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 66
Cys Leu Leu Asp His Val Gly Arg Glu Asn
1 5 10
<210> 67
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 67
Leu Leu Asp His Val Gly Arg Glu Asn Arg
1 5 10
<210> 68
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 68
Leu Asp His Val Gly Arg Glu Asn Arg Gly
1 5 10
<210> 69
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 69
Asp His Val Gly Arg Glu Asn Arg Gly Arg
1 5 10
<210> 70
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 70
His Val Gly Arg Glu Asn Arg Gly Arg Leu
1 5 10
<210> 71
<211> 10
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 71
Val Gly Arg Glu Asn Arg Gly Arg Leu Gly
1 5 10
<210> 72
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 72
Pro Tyr Gly Cys Leu Leu Asp His Val Gly Arg
1 5 10
<210> 73
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 73
Tyr Gly Cys Leu Leu Asp His Val Gly Arg Glu
1 5 10
<210> 74
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 74
Gly Cys Leu Leu Asp His Val Gly Arg Glu Asn
1 5 10
<210> 75
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 75
Cys Leu Leu Asp His Val Gly Arg Glu Asn Arg
1 5 10
<210> 76
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 76
Leu Leu Asp His Val Gly Arg Glu Asn Arg Gly
1 5 10
<210> 77
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 77
Leu Asp His Val Gly Arg Glu Asn Arg Gly Arg
1 5 10
<210> 78
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 78
Asp His Val Gly Arg Glu Asn Arg Gly Arg Leu
1 5 10
<210> 79
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 79
His Val Gly Arg Glu Asn Arg Gly Arg Leu Gly
1 5 10
<210> 80
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 80
Val Gly Arg Glu Asn Arg Gly Arg Leu Gly Ser
1 5 10
<210> 81
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 81
Met Pro Tyr Gly Cys Leu Leu Asp His Val Gly Arg
1 5 10
<210> 82
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 82
Pro Tyr Gly Cys Leu Leu Asp His Val Gly Arg Glu
1 5 10
<210> 83
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 83
Tyr Gly Cys Leu Leu Asp His Val Gly Arg Glu Asn
1 5 10
<210> 84
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 84
Gly Cys Leu Leu Asp His Val Gly Arg Glu Asn Arg
1 5 10
<210> 85
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 85
Cys Leu Leu Asp His Val Gly Arg Glu Asn Arg Gly
1 5 10
<210> 86
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 86
Leu Leu Asp His Val Gly Arg Glu Asn Arg Gly Arg
1 5 10
<210> 87
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 87
Leu Asp His Val Gly Arg Glu Asn Arg Gly Arg Leu
1 5 10
<210> 88
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 88
Asp His Val Gly Arg Glu Asn Arg Gly Arg Leu Gly
1 5 10
<210> 89
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 89
His Val Gly Arg Glu Asn Arg Gly Arg Leu Gly Ser
1 5 10
<210> 90
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 90
Val Gly Arg Glu Asn Arg Gly Arg Leu Gly Ser Gln
1 5 10
<210> 91
<211> 13
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 91
Leu Met Pro Tyr Gly Cys Leu Leu Asp His Val Gly Arg
1 5 10
<210> 92
<211> 13
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 92
Met Pro Tyr Gly Cys Leu Leu Asp His Val Gly Arg Glu
1 5 10
<210> 93
<211> 13
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 93
Pro Tyr Gly Cys Leu Leu Asp His Val Gly Arg Glu Asn
1 5 10
<210> 94
<211> 13
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 94
Tyr Gly Cys Leu Leu Asp His Val Gly Arg Glu Asn Arg
1 5 10
<210> 95
<211> 13
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 95
Gly Cys Leu Leu Asp His Val Gly Arg Glu Asn Arg Gly
1 5 10
<210> 96
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 96
Gln Leu Val Thr Gln Leu Met Tyr Val Met Pro
1 5 10
<210> 97
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 97
Leu Val Thr Gln Leu Met Tyr Val Met Pro Tyr
1 5 10
<210> 98
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 98
Val Thr Gln Leu Met Tyr Val Met Pro Tyr Gly
1 5 10
<210> 99
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 99
Thr Gln Leu Met Tyr Val Met Pro Tyr Gly Cys
1 5 10
<210> 100
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 100
Gln Leu Met Tyr Val Met Pro Tyr Gly Cys Leu
1 5 10
<210> 101
<211> 13
<212> PRT
<213>Artificial sequence (artificial sequences)
<400> 101
Leu Met Tyr Val Met Pro Tyr Gly Cys Leu Leu Asp His
1 5 10

Claims (7)

1. a kind of Antigenic Peptide chain group for treating tumour, which is characterized in that the Antigenic Peptide chain group of the treatment tumour includes SEQ ID No：The combination of any one or at least two amino acid sequences in 1-101.
2. a kind of pharmaceutical composition, which is characterized in that described pharmaceutical composition includes SEQ ID No described in claim 1：1- Any one in 101 or at least two amino acid sequences.
3. pharmaceutical composition according to claim 2, which is characterized in that described pharmaceutical composition is aqueous suspension, solution Or solid state.
4. pharmaceutical composition according to claim 3, which is characterized in that the solid state is uncoated or coated tablet Form.
5. according to the pharmaceutical composition described in any one of claim 2-4, which is characterized in that further include pharmaceutically receive it is auxiliary Material.
6. pharmaceutical composition according to claim 5, which is characterized in that the auxiliary material be excipient, diluent, carrier, In flavoring agent, adhesive and filler any one or at least two combination.
7. Antigenic Peptide chain group the answering in the pharmaceutical composition for preparing treating cancer for the treatment of tumour according to claim 1 With.
CN201810584274.8A 2018-06-08 2018-06-08 A kind of Antigenic Peptide chain group for treating tumour and its application in drug Withdrawn CN108715603A (en)

Priority Applications (1)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1597953A (en) * 1995-03-31 2005-03-23 华盛顿大学 Intracellular domain of the her-2/neu protein for prevention or treatment of maligancies
WO2016202963A2 (en) * 2015-06-19 2016-12-22 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy and methods for generating scaffolds for the use against pancreatic cancer and other cancers

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1597953A (en) * 1995-03-31 2005-03-23 华盛顿大学 Intracellular domain of the her-2/neu protein for prevention or treatment of maligancies
WO2016202963A2 (en) * 2015-06-19 2016-12-22 Immatics Biotechnologies Gmbh Novel peptides and combination of peptides for use in immunotherapy and methods for generating scaffolds for the use against pancreatic cancer and other cancers

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
WANG 等: "Human tumor antigens for cancer vaccine development", 《IMMUNOLOGICAL REVIEWS》 *
杨帆 等: "肿瘤抗原肽及CTL杀伤机理的研究进展", 《中国肿瘤》 *

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