CN108440646A - 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
CN108440646A
CN108440646A CN201810284757.6A CN201810284757A CN108440646A CN 108440646 A CN108440646 A CN 108440646A CN 201810284757 A CN201810284757 A CN 201810284757A CN 108440646 A CN108440646 A CN 108440646A
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artificial sequence
prt
val gly
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cell
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刘玉强
霍冲
孙旭东
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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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • Genetics & Genomics (AREA)
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  • Pharmacology & Pharmacy (AREA)
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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 94.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 is the new treatment side of future therapeutic tumour by body immune system killing tumor cell Method has been increasingly becoming the hot spot for the treatment of tumour.The CIK that the method for the tumour of biological immune treatment at present is more including common is thin Born of the same parents' immunization therapy, DC medications treatment etc., but its therapeutic effect is not notable, and survival is not improved significantly.Separately have With the immunocyte medication that not mutated tumour high-expression albumen stimulates, research has anti tumor immune response, but since its is non-specific Property 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, Antigenic Peptide chain group of the invention can induce the blastomogenic Dendritic Cells of production, thus as antigen presenting cell Dendritic Cells antigenic information can be presented to T cell, to T cell interact, make T cell generate specific killing Tumour cell plays the role of killing tumor cell.
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 1-94, such as can be SEQ ID No： Any one in 1-94, it is two arbitrary, three arbitrary, four arbitrary, it is arbitrary five until arbitrary 93 or all 94 Combination, 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 1-94 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 End 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 any one in excipient, diluent, carrier, flavoring agent, adhesive and filler Or at least two combination, such as can be excipient, carrier and diluent, flavoring agent, adhesive and filler, or dilution Agent, the combination of carrier, flavoring agent, adhesive and filler, due to the limitation of length, the form of all combinations no longer arranges one by one It lifts.
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 in 7.4PBS (Hyclone) solution that the Antigenic Peptide chain group of the treatment tumour, which is dissolved in pH value, and concentration is adjusted to Covering 5%Aldara cream (iNova Pharmaceuticals after 200ug are subcutaneously injected in 2.5mg/ml, each upper arm Australia Pty Ltd.), once a week, 12 weeks are a cycle.
(2) stimulated in vitro method：
0th day：
(1) COBE Spectra blood analysis systems (U.S. Caridian BCT, Inc.) are used to carry out monocyte point From acquisition filter blood volume 2500-3500ml；(2) preparation 1LDC-CM culture solutions, 500mlX2 parts；(3) by cell from 4 centrifuge tubes It is transferred in 500ml centrifuge tubes, is used in combination 10mlDC-CM to rinse former centrifuge tube, and be transferred to 500ml centrifuge tubes, covers, mixing；(4) With 25ml suction pipes, add 15mlDC-CM to each culture bottle；(5) it is all 1000IU/ml the concentration of IL-4 and GM-CSF to be added； (6) IL-4 is diluted, with 1%HAS to 1000IU/ml inside PBS.
6th day：The ripe mixed liquor of addition
(7) with 1%HSA-PBS dilutions IL-1 β, INF- α, IL-6 to 25ug/ml；(8) final 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) nothing is used Bacterium suction pipe inhales 1ml and contains the DC-CM of cell factor to each culture bottle；(11) culture bottle be put into incubator (37 DEG C, 5% CO2；± 10 DEG C, ± 0.5%CO2)。
The 7-8 days：Prepare peptide chain pulse culture solution (PPM)
(12) amount of the PPM needed is calculated：The amount for the PPM that culture bottle quantity X30ml+300ml=needs；It (13) will culture Bottle takes out from incubator, and bottle inner cell is transferred to 500ml sterile centrifugation tubes；(14) culture bottle is rinsed with 30mlPPM, and punching Washing lotion is transferred to 500ml centrifuge tubes；(15) all supernatants are shifted with 2ml suction pipes, are used in combination 25mlPPM that cell is resuspended, by harvest Harvest pipe DC cells and flush pipe DC cells are merged into same pipe, indicate：DC cell pipes；(16) one group that 1 pipe freezes is taken out Body specific mutations peptide chain dissolves peptide chain with DC-PPM；(17) add peptide chain to DC pipes, a concentration of 5ug/ml；(18) after pine lid Be put into incubator (37 DEG C, 5%CO2；± 10 DEG C, ± 0.5%CO2), per 30min, taking-up incubator, mixing, total time 1.5 are small When；(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) remove supernatant with 2ml suction pipes；(22) individuation specificity DC cells are harvested, It 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：
The present invention provides a kind of Antigenic Peptide chain group for treating tumour and its application in drug, the treatment tumour Antigenic Peptide chain group includes SEQ ID No：The combination of any one or at least two amino acid sequences in 1-94.The present invention's is anti- Former peptide chain group can induce the blastomogenic Dendritic Cells of production, thus can believe antigen as the Dendritic Cells of antigen presenting cell Breath is presented to T cell, to interact with T cell, so that T cell is generated specific killing tumour cell, plays killing tumour The effect of cell.After medication at least 6 weeks, it can obviously observe that tumour largely disappears by instrument, density is thin out, and 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, 71 years old, adenocarcinoma of lung, brain metastes, the clinical IV phases were in progress after GP chemotherapy 6 times, and the molecular targeted medicines of KRAS are resistance to Medicine.Pulmonary lesions tissue biopsy is taken, after carrying out full exon sequencing and the detection of HLA typing chips, patient carries KRAS p.G12S Mutation, HLA partings are HLA-A：A*3101A*3101；HLA-B:B*3217B*3102；HLA-C：C*3201C*0612；HLA- DQB1：DQB1*0218DQB1*1231；HLA-DRB1：DRB1*0101DRB1*0231.
Use the specific tumor antigen peptide chain combined therapy of the present invention, 1 times a week, totally 12 weeks.Detect injections of antigens peptide Spot detection specific C D8+Tetramer+T cells secrete situation before and after chain group (hereinafter referred to as " medication "), and pass through image Tumor size variation in 12 weeks before and after observing medication is learned, as a result as depicted in figs. 1 and 2.Specific peptide chain selection is as follows：SEQ ID No：1.
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 3.52%；Figure 1-C is 12 weeks after stain chromatic graphs of medication, CD8+Tetramer+T a concentration of 4.8%；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 lung tumors CT figures before and after medication, and wherein Fig. 2-A are CT figures before medication, to swell under the arch of aorta in vertical diaphragm Tumor, the greater 4cm × 3cm；Fig. 2-B are that CT schemes after medication 6 weeks, it can be seen that tumour disappears substantially, and front and back variation is apparent.
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, female, 68 years old, adenocarcinoma of lung, Bone tumour took orally Gefitinib drug resistance；Carry out full exon sequencing and HLA points After cake core detection, patient carries KRASp.G12S mutation, and HLA partings are HLA-A：A*0602A*0201；HLA-B:B* 0206B*3201；HLA-C：C*0106C*0206；HLA-DQB1：DQB1*0602DQB1*0230；HLA-DRB1：DRB1* 0224DRB1*1222。
It is combined treatment using the Antigenic Peptide chain group of the treatment tumour of the present invention, 1 times a week, totally 12 weeks.Specific choice Peptide chain it is as follows：SEQ ID No：2.
Pretherapy and post-treatment lung tumors size variation situation is as shown in figure 3, as seen from Figure 3, before medication treatment, inferior lobe of right lung is swollen Tumor size 4cm × 3cm (Fig. 3-A)；11 weeks after medication treatment, inferior lobe of right lung tumour disappears substantially, only 1cm × 1cm (Fig. 3- B), for tumour compared with being obviously reduced before medication, density is thin out.This example demonstrates that the Antigenic Peptide chain group of the present invention can induce generation tumour Dendritic Cells, antigenic information can be presented to T cell by the Dendritic Cells as antigen presenting cell, mutual with T cell Effect makes T cell generate specific killing tumour cell, plays the role of killing tumor cell, and with obvious effects.
Embodiment 3-94
Embodiment 3-94 takes variety classes, different degrees of cancer patient to carry out full exon sequencing and HLA typing chips After detection, patient is to carry KRAS p.G12S mutation patients, is carried out respectively using the combining form of different Antigenic Peptide chain groups Treatment, once a week, totally 12 weeks.HLA*A3101-HVKITDFGR Tetramer coloration results of embodiment 3-94 and treatment Front and back lung tumors size variation situation is similar with embodiment 1-2, and due to the limitation of length, it is no longer repeated herein.More than As a result the Antigenic Peptide chain group that the present invention can be explained can induce the blastomogenic Dendritic Cells of production, the tree as antigen presenting cell Antigenic information can be presented to T cell by prominent shape cell, be interacted 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, and with obvious effects.
During being treated to embodiment 1-94, with before ELISA detections antigen peptide chain, medication 3 weeks, 7 weeks, 11 weeks Specific IFN-γ secretion situation, concrete outcome are 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 KRAS P.G12S is mutated patient) treat during, before detecting medication with ELISA, medication 3 weeks, 7 weeks, 11 weeks specific IFN-γ Situation is secreted, concrete outcome is as shown in table 2, and dosage is identical as embodiment 1-94；Wherein, comparative example 1-5 is added without peptide chain.
From table 2 it can be seen that embodiment 1-94,11 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 1-94, illustrate that it does not increase the tumor-killing ability of peripheral blood in patients or the ability of blood killing tumour is far below Embodiment 1-94 further demonstrates the effect of the present invention.
Table 2IFN- γ secretion statistics lists
Then, the rate of side effects of embodiment 1-94 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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<213>Artificial sequence (artificial sequence)
<400> 44
Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile
1 5 10
<210> 45
<211> 11
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 45
Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln
1 5 10
<210> 46
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 46
Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Ser
1 5 10
<210> 47
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 47
Thr Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly
1 5 10
<210> 48
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 48
Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val
1 5 10
<210> 49
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 49
Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly
1 5 10
<210> 50
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 50
Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys
1 5 10
<210> 51
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 51
Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser
1 5 10
<210> 52
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 52
Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala
1 5 10
<210> 53
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 53
Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu
1 5 10
<210> 54
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 54
Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr
1 5 10
<210> 55
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 55
Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile
1 5 10
<210> 56
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 56
Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln
1 5 10
<210> 57
<211> 12
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 57
Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu
1 5 10
<210> 58
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 58
Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val
1 5 10
<210> 59
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 59
Thr Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly
1 5 10
<210> 60
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 60
Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys
1 5 10
<210> 61
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 61
Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser
1 5 10
<210> 62
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 62
Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala
1 5 10
<210> 63
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 63
Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu
1 5 10
<210> 64
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 64
Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr
1 5 10
<210> 65
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 65
Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile
1 5 10
<210> 66
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 66
Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln
1 5 10
<210> 67
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 67
Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu
1 5 10
<210> 68
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 68
Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile
1 5 10
<210> 69
<211> 14
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 69
Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln
1 5 10
<210> 70
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 70
Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly
1 5 10 15
<210> 71
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 71
Thr Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys
1 5 10 15
<210> 72
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 72
Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser
1 5 10 15
<210> 73
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 73
Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala
1 5 10 15
<210> 74
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 74
Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu
1 5 10 15
<210> 75
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 75
Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr
1 5 10 15
<210> 76
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 76
Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile
1 5 10 15
<210> 77
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 77
Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln
1 5 10 15
<210> 78
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 78
Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu
1 5 10 15
<210> 79
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 79
Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile
1 5 10 15
<210> 80
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 80
Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln
1 5 10 15
<210> 81
<211> 15
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 81
Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn
1 5 10 15
<210> 82
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 82
Met Thr Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys
1 5 10 15
<210> 83
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 83
Thr Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser
1 5 10 15
<210> 84
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 84
Glu Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala
1 5 10 15
<210> 85
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 85
Tyr Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu
1 5 10 15
<210> 86
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 86
Lys Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr
1 5 10 15
<210> 87
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 87
Leu Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile
1 5 10 15
<210> 88
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 88
Val Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln
1 5 10 15
<210> 89
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 89
Val Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu
1 5 10 15
<210> 90
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 90
Val Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile
1 5 10 15
<210> 91
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 91
Gly Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln
1 5 10 15
<210> 92
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 92
Ala Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn
1 5 10 15
<210> 93
<211> 16
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 93
Ser Gly Val Gly Lys Ser Ala Leu Thr Ile Gln Leu Ile Gln Asn His
1 5 10 15
<210> 94
<211> 17
<212> PRT
<213>Artificial sequence (artificial sequence)
<400> 94
Lys Ile Pro Val Ala Ile Lys Glu Arg Glu Ala Thr Ser Pro Lys Ala
1 5 10 15
Asn

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 1-94.
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 94 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.
CN201810284757.6A 2018-04-02 2018-04-02 A kind of Antigenic Peptide chain group for treating tumour and its application in drug Withdrawn CN108440646A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111393504A (en) * 2020-03-18 2020-07-10 北京鼎成肽源生物技术有限公司 Liver cancer antigen composition, application thereof and cytotoxic T lymphocyte
CN112110995A (en) * 2019-06-19 2020-12-22 上海交通大学医学院 Tumor neoantigen polypeptide and application thereof
WO2021170684A1 (en) * 2020-02-24 2021-09-02 Oblique Therapeutics Ab Kras epitopes and antibodies

Citations (2)

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Publication number Priority date Publication date Assignee Title
CN101448848A (en) * 2006-03-27 2009-06-03 全球免疫股份有限公司 Ras mutation and compositions and mehods related thereto
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)

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Publication number Priority date Publication date Assignee Title
CN101448848A (en) * 2006-03-27 2009-06-03 全球免疫股份有限公司 Ras mutation and compositions and mehods related thereto
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

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112110995A (en) * 2019-06-19 2020-12-22 上海交通大学医学院 Tumor neoantigen polypeptide and application thereof
WO2021170684A1 (en) * 2020-02-24 2021-09-02 Oblique Therapeutics Ab Kras epitopes and antibodies
CN111393504A (en) * 2020-03-18 2020-07-10 北京鼎成肽源生物技术有限公司 Liver cancer antigen composition, application thereof and cytotoxic T lymphocyte
CN111393504B (en) * 2020-03-18 2023-03-31 北京鼎成肽源生物技术有限公司 Liver cancer antigen composition, application thereof and cytotoxic T lymphocyte

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Application publication date: 20180824