CN108047309A - A kind of Antigenic Peptide chain group for treating tumour and its application in drug - Google Patents

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 27.The Antigenic Peptide chain group of the present invention can induce the blastomogenic Dendritic Cells of production, thus antigenic information can be presented to T cell by the Dendritic Cells as antigen presenting cell, so as to interact with T cell, T cell is made to generate specific killing tumour cell, plays 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 more particularly to a kind of for tumour individuation biology the invention belongs to malignant tumour biological immune technical field of pharmaceuticals The Antigenic Peptide chain group of immunization therapy and its application in drug.

Background technology

At present, global Cancer Mortality rises increasingly, and 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, stomach 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 method of the tumour of biological immune treatment at present is more, thin including common CIK 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..

The essence of biological immune treatment is mainly by body immune system come killing tumor cell, is made wherein directly playing It is killer T cell, and Dendritic Cells (DCs) is antigen presenting cell (APCs), major function is by antigenic information Offer to T cell.It is believed that some autoimmune responses are since microenvironment tissue damage causes local DC to activate, then It interacts with T cell, so as to trigger immune response.Therefore, DCs triggers the ability of t cell response to can be used for tumour medication In.The related high expressing protein induction of some tumours of external use generates DCs, and defeated time patient's body, and it is relatively special to be used as tumour Induced t cell in APCs.Animal model has confirmed that DC tumour medications reverse the anergy of T cell and cause to connect The anti-tumor effect got off.However, the related high expressing protein of tumour induces the DCs generated and do not have stringent specificity, swell Histocyte beyond knurl also expresses same albumen, and therefore, side reaction is a problem.

Tumour is the unlimited hyperplasia of cell as a result, and the growth of cell is by gene-determined.There are tumours in human body Gene and the different gene group of two big function of tumor suppressor gene.Tumour is due to the up-regulation of oncogene function, tumour The suppressed result of suppressor function.Various extraneous factors are by gene such as radioactive ray, carcinogenic chemicals, virus etc. Change and carry out induced tumors, the change of gene includes the various DNA damages such as base mutation, base crosslinking, DNA break, DNA missings Wound.Gene therapy is the biomedical treatment based on the inhereditary material for changing people, is by the normal gene of people or has treatment The gene of effect imports human body target cell by certain way, directly against the root of disease --- and abnormal gene is sent out in itself Therapeutic effect is waved, so as to achieve the purpose that treat disease；Gene therapy product enters generates target protein or more again after cell Peptide, so as to play special biological therapy effect.Clinical experiments have proved that the effect of gene therapy, is higher than simple Radiotherapy chemotherapy curative effect Go out several times；When treating non-small cell carcinoma, 60% patient tumors disappear completely or partial remission；The effect of to breast cancer is even more height Up to 90%.

The content of the invention

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, so as 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 1-27, such as can be SEQ ID No： Any one in 1-27, it is two arbitrary, three arbitrary, four arbitrary, it is arbitrary five until arbitrary 26 or all 27 Combination, since the limitation of length is no longer all enumerated herein.

Particular sequence is as follows：

SEQ ID No：1——STVQLIM

SEQ ID No：2——TVQLIMQ

SEQ ID No：3——VQLIMQL

SEQ ID No：4——QLIMQLM

SEQ ID No：5——LIMQLMP

SEQ ID No：6——IMQLMPF

SEQ ID No：7——MQLMPFG

SEQ ID No：8——STVQLIMQ

SEQ ID No：9——LIMQLMPF

SEQ ID No：10——IMQLMPFG

SEQ ID No：11——TSTVQLIMQ

SEQ ID No：12——QLIMQLMPF

SEQ ID No：13——MQLMPFGCL

SEQ ID No：14——CLTSTVQLIM

SEQ ID No：15——VQLIMQLMPF

SEQ ID No：16——QLIMQLMPFG

SEQ ID No：17——ICLTSTVQLIM

SEQ ID No：18——TSTVQLIMQLM

SEQ ID No：19——STVQLIMQLMP

SEQ ID No：20——TVQLIMQLMPF

SEQ ID No：21——VQLIMQLMPFG

SEQ ID No：22——QLIMQLMPFGC

SEQ ID No：23——GICLTSTVQLIM

SEQ ID No：24——TSTVQLIMQLMP

SEQ ID No：25——TVQLIMQLMPFG

SEQ ID No：26——IMQLMPFGCLLD

SEQ ID No：27——MQLMPFGCLLDY

Second aspect, the present invention provide a kind of pharmaceutical composition, and described pharmaceutical composition is included as described in relation to the first aspect SEQ ID No：Any one in 1-27 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 other substances in the dry state, 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 can include containing inert diluent such as water, ethyl alcohol, glycerine, vegetable oil or atoleine Pharmaceutically useful solution, suspension, emulsion, syrup and elixir.Described pharmaceutical composition can also be included in addition to diluent Other liquid substances, such as wetting agent, sweetener, thickener, flavoring agent or stabilizer product.

Preferably, the auxiliary material pharmaceutically received is further included.

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, so as to interact with T cell, T cell is made to generate specific killing tumour cell, so as 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, stomach 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 Knurl, 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 in given treatment with other drugs or with putting Penetrate therapy or operation joint.Specifically used method is：

(1) internal stimulus method：

The Antigenic Peptide chain group of the treatment tumour is dissolved in pH value as in 7.4PBS (Hyclone) solution, concentration is adjusted to 2.5mg/ml, each upper arm cover 5%Aldara cream (iNovaPharmaceuticals after 200ug is subcutaneously injected Australia Pty Ltd.), once a week, 12 weeks are a cycle.

(2) stimulated in vitro method：

(1) the 0th day

Monocyte separation is carried out using COBE Spectra blood analysis systems (Caridian BCT, Inc.) to gather Hemofiltration amount 2500-3500ml；Prepare the sterile samples of 2ml, 1ml is divided to carry out cell count, and carries out Activity determination (streaming/7- ADD)；Calculate the volume of separation DC cell samples：Total karyocyte 7 × 10⁹/ calculating concentration；Cell is transferred to the transfer of 300ml In bag, GMP laboratories are transferred to；Prepare 1L DC-CM culture solutions, 500ml × 2 part；With the syringe holder sample of 60ml from transfer Bag removes, and is divided in the centrifuge tube of 4 200ml；Often pipe adds in 100-150ml HBSS, closes lid, and gently mixing；Drop Speed centrifugation, 15min, 800rpm (137Xg), room temperature；With the sterile pipette tips transfer supernatants of 2ml, cell is resuspended in 100- 150mlHBSS, capping, mixing；Low-speed centrifugal 10min, 1000rpm (214Xg), room temperature；With the sterile pipette tips transfer supernatants of 2ml Cell is resuspended in 30ml DC-CM culture solutions in liquid；Cell is transferred to from 4 centrifuge tubes in 500ml centrifuge tubes, and uses 10ml DC-CM rinses former centrifuge tube, and is transferred to 500ml centrifuge tubes, covers, mixing；With 3ml syringe transferase 10 .5ml to 12 × 75mm In tubule, counted；Calculate the blake bottle number needed：TNC/1.75×10⁸=blake bottle the number needed；Calculate DC-CM's Volume requirement：(it is added to the volume 1.75 × 10 of diluting cells⁷/ml)：The quantity that blake bottle needs × 10ml DC-CM=are needed The DC-CM volumes wanted；With 25ml suction pipes, add 15ml DC-CM to each blake bottle；With 10ml or 25ml suction pipes, add 10ml weights The sample (1.75 × 10 hanged⁷/ ml) to each blake bottle, it is tamping with lid；Blake bottle is shaken up, liquid is made to be paved with entire bottle Bottom；Blake bottle is put into incubator (37 DEG C, 5%CO₂；± 10 DEG C, ± 0.5%CO₂), 2 it is small when 30min ±, cell is allowed to paste Wall；IMDM be put into incubator (37 DEG C, 5%CO₂；± 10 DEG C, ± 0.5%CO₂), rinse blake bottle 2 times with 35ml IMDM；It needs The IMDM volumes wanted=blake bottle quantity × 70ml IMDM；It rinses after blake bottle, adds the DC-CM of 50ml cell factors：It needs IMDM=blake bottles quantity × 50ml；The concentration for adding in IL-4 and GM-CSF is all 1000IU/ml；IL-4 is diluted, with 1% HAS is inside PBS to 1000IU/ml；5-10 blake bottle is operated every time to reduce the time being exposed in air；Blake bottle It is taken out from incubator, jiggles blake bottle；Blow adherent cell off with 2ml suction pipes；35ml temperature IMDM is cultivated to each Bottle, pays attention to：Add from the acellular one side of bottle wall.A loose lower bottle cap, gently precious jade blake bottle, makes still adherent cell get off.Gently Light precious jade blake bottle, avoids cell from being attached on wall.It is laid flat blake bottle.With 2ml suction pipes, IMDM is shifted, pays attention to tilting blake bottle.With 35mlIMDM is rinsed once again.Add the DC-CM that 50ml contains cell factor to each blake bottle, capping.Gently it is laid flat culture Bottle, makes liquid cover bottom of bottle.Blake bottle be put into incubator (37 DEG C, 5%CO₂；± 10 DEG C, ± 0.5%CO₂)。

(2) the 6th days：The ripe mixed liquor of addition

With 1%HSA-PBS dilutions IL-1 β, INF- α, IL-6 to 25ug/ml；If blake bottle quantity is less than 50,50 are prepared The cell factor of a blake bottle；Final concentration：IL-1β10ng/ml、INF-α10ng/ml、IL-615ng/ml.The diluting cells factor In 44mlDC-CM, until last volume 50ml.1ml, which is inhaled, with aseptic straw contains the DC-CM of cell factor to each blake bottle. Liquid in mixing blake bottle (after adding in cell factor).Blake bottle be put into incubator (37 DEG C, 5%CO₂；± 10 DEG C, ± 0.5%CO₂)。

(3) the 7-8 days：Prepare peptide chain pulse culture solution (PPM)

Calculate the amount of the PPM needed：The amount for the PPM that blake bottle quantity X30ml+300ml=needs；By blake bottle from culture Case takes out, and bottle inner cell is transferred to 500ml sterile centrifugation tubes.It (pours into 25ml suction pipes or directly, 3 blake bottles are transferred to one A 500ml centrifuge tubes).It is counted with suction pipe suction 1ml to 12 × 75mm pipes, and carries out mycoplasma, Chlamydia detection.Reduction of speed from Heart 1200rpm (309Xg), 7min, room temperature (if multiple pipes, centrifuge) simultaneously.Blake bottle is rinsed with 30ml PPM, and flushing Liquid is transferred to 500ml centrifuge tubes.Reduction of speed centrifugal elutriation liquid, 1200rpm (309Xg), 7min, room temperature.Flushing liquor is removed with 2ml suction pipes With the supernatant of harvest pipe, cell is resuspended with 10ml PPM.Transfer harvests pipe DC cells to a new 200ml centrifuge tube.Turn Flush pipe DC cells are moved to a new 200ml centrifuge tube.Reduction of speed centrifuges, 1200rpm (309Xg), 7min, room temperature；It is inhaled with 2ml Pipe shifts all supernatants, and cell is resuspended with 25ml PPM, and the harvest pipe DC cells of harvest and flush pipe DC cells are merged Enter same pipe, indicate：DC cell pipes.Capping centrifuges simultaneously mixing.One group of individuation specific mutations peptide chain that 1 pipe freezes is taken out, Peptide chain is dissolved with DC-PPM.Add peptide chain to DC pipes, concentration 5ug/ml.Pine lid after be put into incubator (37 DEG C, 5%CO₂；±10 DEG C, ± 0.5%CO₂), incubator, mixing, when total time 1.5 is small are taken out per 30min.The DC cells that 0.2ml is taken to be resuspended, transfer Into 12 × 75mm pipes, endotoxin check and evaluation is carried out.Reduction of speed centrifuges, 1200rpm (309Xg), 7min, room temperature.With 2ml suction pipes Remove supernatant.Individuation specificity DC cells are harvested, counts and is dissolved in 1ml PBS solutions.Tumor-draining lymphode or Injection in other.

Compared with prior art, provided by the present invention for tumour individuation biological immune treatment Antigenic Peptide chain group at least 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 1-27.The present invention's is anti- Former peptide chain group can induce the blastomogenic Dendritic Cells of production, thus the Dendritic Cells as antigen presenting cell can believe antigen Breath is presented to T cell, so as to interact with T cell, T cell is made to generate specific killing tumour cell, plays killing tumour The effect of cell.After medication at least 6 weeks, it can substantially 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 embodiment

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, 47 years old.Squamous cell lung carcinoma, hepatic metastases, clinical IV phases, lung tumors I125 seeds implanted treatment 1 It is secondary, it is in progress after gemcitabine list medicine chemotherapy 3 times, is in progress after diagnosis of hepatic metastases chemoembolization, the molecular targeted medicine drug resistances of EGFR.Lung Interior multiple transfer, hepatic metastases, pleura metastasis, Bone tumour, Coeliac lymphadenectomy.Pulmonary lesions tissue biopsy is taken, is carried out complete outer After aobvious son sequencing and the detection of HLA typing chips, it is HLA-A that patient, which carries EGFR p.T790M, HLA parting,：A*0216A*3002； HLA-B:B*1502B*5801；HLA-C：C*0303C*1203；HLA-DQB1：DQB1*0401DQB1*0602；HLA-DRB1： DRB1*1101DRB1*1501。

Use the specific tumor antigen peptide chain combined therapy of the present invention, 1 times a week, totally 6 weeks.Detect injections of antigens peptide chain Spot detection specific C D8+Tetramer+T cells secrete situation and pass through iconography before and after group (hereinafter referred to as " medication ") The tumor size variation of 6 weeks before and after observation medication, as a result as depicted in figs. 1 and 2.Specific peptide chain selection is as follows：

a)TVQLIMQ

b)LIMQLMP

c)STVQLIMQ

d)LIMQLMPF

e)TSTVQLIMQ

f)QLIMQLMPF

g)CLTSTVQLIM

h)QLIMQLMPFG

i)ICLTSTVQLIM

j)TVQLIMQLMPF

k)TVQLIMQLMPFG

Fig. 1 be HLA*A3101-HVKITDFGR Tetramer colored graphs, wherein, Fig. 1-A be medication before colored graph, CD8 + Tetramer+T concentration is 1.5%；Fig. 1-B are 3 weeks after stain chromatic graphs of medication, and CD8+Tetramer+T concentration is 1.7%；Fig. 1-C For 6 weeks after stain chromatic graphs of medication, CD8+Tetramer+T concentration is 3.8%；As can be seen that amount of speckle has substantially from three group pictures Raised variation tendency illustrates that the ratio (concentration) of tumor-killing cell CD8+Tetramer+T in blood significantly improves.

Fig. 2 be medication before and after lung tumors CT scheme, wherein Fig. 2-A be medication before CT scheme, mediastinum tumor area for 2cm × 3cm；Fig. 2-B scheme for CT after medication 6 weeks, it can be seen that tumour disappears substantially.

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, generate T cell special Property killing tumor cell, plays the role of killing tumor cell, and with obvious effects.

Embodiment 2

Patient B, man, 70 years old, right lung gland cancer, multiple lymphatic metastasis, no operative indication, pemetrexed+Cisplatin 6 week of chemotherapy, pemetrexed chemotherapy are in progress after 1 cycle, are in progress after I125 brachytherapy.Carry out full extron sequencing and After the detection of HLA typing chips, the results show patient carries EGFRp.T790M mutation, and HLA partings are HLA-A：A*0202A* 0212；HLA-B:B*0702B*0808；HLA-C：C*0401C*0701；HLA-DQB1：DQB1*030302DQB1*0601；HLA- DRB1：DRB1*0401DRB1*1002.

Treatment is combined 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：

a)MQLMPFGCLLDY

b)TSTVQLIMQLMP

c)GICLTSTVQLIM

d)TSTVQLIMQLM

e)QLIMQLMPFGC

f)VQLIMQLMPF

g)QLIMQLMPF

h)IMQLMPFG

i)MQLMPFG

j)MQLMPFGCL

Pretherapy and post-treatment lung tumors size variation situation is as shown in figure 3, as seen from Figure 3, before medication treatment, right lung tumour is big Small 4 × 6cm (Fig. 3-A)；3 weeks after medication treatment, right lung tumour disappears (Fig. 3-B) substantially, and tumour is close compared with being obviously reduced before medication It spends thin out.This example demonstrates that the Antigenic Peptide chain group of the present invention can induce the blastomogenic Dendritic Cells of production, as antigen presentation Antigenic information can be presented to T cell by the Dendritic Cells of cell, be interacted with T cell, and T cell is made to generate specific killing Tumour cell plays the role of killing tumor cell, and with obvious effects.

Embodiment 3-50

Embodiment 3-50 takes variety classes, different degrees of cancer patient, respectively using the group of different Antigenic Peptide chain groups Conjunction form is treated, once a week, totally 12 weeks.HLA*A3101-HVKITDFGR Tetramer dyeing of embodiment 3-50 As a result it is similar with embodiment 1-2 with pretherapy and post-treatment lung tumors size variation situation, due to the limitation of length, it is not repeated herein It repeats.The Antigenic Peptide chain group that the present invention can be explained in result above can induce the blastomogenic Dendritic Cells of production, be in as antigen Antigenic information can be presented to T cell by the Dendritic Cells of delivery cell, be interacted with T cell, and T cell is made to generate specificity and is killed Hinder tumour cell, play the role of killing tumor cell, and it is with obvious effects.

During being treated to embodiment 1-50, 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

During being treated to comparative example 1-10, before detecting medication with ELISA, medication 3 weeks, 7 weeks, the specificity of 11 weeks IFN-γ secretion situation, concrete outcome is as shown in table 1, and dosage is identical with embodiment 1-50；Wherein, comparative example 1-5 is added without Peptide chain.

As it can be seen from table 1 embodiment 1-50,11 weeks after medication, the specific IFN-γ level of T cell secretion has Significantly raised trend, illustrate to have used any one in Antigenic Peptide chain group of the invention or its any combination 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 1-50, 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 1-50 further demonstrates the effect of the present invention.

Table 1IFN- γ secretion statistics lists

Then, the rate of side effects of embodiment 1-50 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 understand, the feelings of the spirit and scope of the present invention required by appended claims are not departed from 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 from the limitation of given any specific exemplary teachings.

Applicant states, made for the present invention further specifically the above content is specific preferred embodiment is combined It is bright, it is impossible to assert that the specific implementation of the present 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, several simple deduction or replace can also be made, should all be considered as category In protection scope of the present invention.

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 1-27.

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 27 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 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 for 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.