CN108409832A - 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 PDFInfo
- Publication number
- CN108409832A CN108409832A CN201810184638.3A CN201810184638A CN108409832A CN 108409832 A CN108409832 A CN 108409832A CN 201810184638 A CN201810184638 A CN 201810184638A CN 108409832 A CN108409832 A CN 108409832A
- Authority
- CN
- China
- Prior art keywords
- cell
- tumour
- peptide chain
- seq
- chain group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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 34.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
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..
The essence of biological immune treatment is made wherein directly playing mainly by body immune system come killing tumor cell
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 certain autoimmune responses are since microenvironment tissue damage causes local DC to activate, then
It interacts with T cell, to cause immune response.Therefore, the ability of DCs initiations t cell response can be used for tumour medication
In.The related high protein induced generation DCs of expression of some tumours of external use, and defeated time patient's body, it is relatively special to be used as tumour
Induced t cell in APCs.Animal model has confirmed that DC tumour medications make the anergy of T cell reverse and cause to connect
The anti-tumor effect got off.However, the related height of tumour expresses the DCs of protein induced generation and do not have stringent specificity, swell
Histocyte other than tumor also expresses same albumen, and therefore, side reaction is a problem.
Tumour is cell without limitation hyperplasia 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 such as radioactive ray, carcinogenic chemicals, virus etc. are by gene
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 the normal gene by people or has a treatment
The gene of effect by certain way import human body target cell, directly against the root of disease --- abnormal gene itself and send out
Therapeutic effect is waved, to achieve the purpose that treat disease；Gene therapy product enters generates target protein or more again after cell
Peptide, 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 subside completely or partial remission；The effect of to breast cancer is even more height
Up to 90%.
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 1-34, such as can be SEQ ID No：
Any one in 1-34, it is two arbitrary, three arbitrary, four arbitrary, it is arbitrary five until arbitrary 33 or all 34
Combination, since the limitation of length is no longer all enumerated herein.
Particular sequence is as follows：
SEQ ID No：1——PVAIKES
SEQ ID No：2——IPVAIKES
SEQ ID No：3——KIPVAIKES
SEQ ID No：4——VKIPVAIKES
SEQ ID No：5——KVKIPVAIKES
SEQ ID No：6——EKVKIPVAIKES
SEQ ID No：7——VAIKESP
SEQ ID No：8——PVAIKESP
SEQ ID No：9——IPVAIKESP
SEQ ID No：10——KIPVAIKESP
SEQ ID No：11——VKIPVAIKESP
SEQ ID No：12——KVKIPVAIKESP
SEQ ID No：13——AIKESPK
SEQ ID No：14——VAIKESPK
SEQ ID No：15——PVAIKESPK
SEQ ID No：16——IPVAIKESPK
SEQ ID No：17——KIPVAIKESPK
SEQ ID No：18——VKIPVAIKESPK
SEQ ID No：19——IKESPKA
SEQ ID No：20——AIKESPKA
SEQ ID No：21——VAIKESPKA
SEQ ID No：22——PVAIKESPKA
SEQ ID No：23——IPVAIKESPKA
SEQ ID No：24——KIPVAIKESPKA
SEQ ID No：25——KESPKAN
SEQ ID No：26——IKESPKAN
SEQ ID No：27——AIKESPKAN
SEQ ID No：28——VAIKESPKAN
SEQ ID No：29——PVAIKESPKAN
SEQ ID No：30——IPVAIKESPKAN
SEQ ID No：31——ESPKANK
SEQ ID No：32——KESPKANK
SEQ ID No：33——IKESPKANK
SEQ ID No：34——AIKESPKANK
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 1-34 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：
(1) the 0th day
Monocyte separation is carried out using COBE Spectra blood analysis systems (Caridian BCT, Inc.) to acquire
Hemofiltration amount 2500-3500ml；Prepare the sterile samples of 2ml, divides 1ml to carry out cell count, and carry out Activity determination (streaming/7-
ADD)；Calculate the volume of separation DC cell samples：Total karyocyte 7 × 109/ calculate concentration；Cell is transferred to the transfer of 300ml
In bag, it is transferred to the laboratories GMP；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 100-150ml HBSS are added in pipe, close lid, and gently mixing；Drop
Speed centrifugation, 15min, 800rpm (137Xg), room temperature；Supernatant is shifted with the sterile pipette tips of 2ml, cell is resuspended in 100-150ml
HBSS, capping, mixing；Low-speed centrifugal 10min, 1000rpm (214Xg), room temperature；Supernatant is shifted with the sterile pipette tips of 2ml, is resuspended
Cell is in 30ml DC-CM culture solutions；Cell is transferred to from 4 centrifuge tubes in 500ml centrifuge tubes, 10ml DC-CM are used in combination
Former centrifuge tube is rinsed, and is transferred to 500ml centrifuge tubes, is covered, mixing；0.5ml is shifted to 12 × 75mm tubules with 3ml syringes
It is interior, it is counted；Calculate the culture bottle number needed：TNC/1.75×108=culture bottle the number needed；Calculate the volume of DC-CM
Requirement：(it is added to the volume 1.75 × 10 of diluting cells7/ml)：The quantity that culture bottle needs × 10ml DC-CM=need
DC-CM volumes；With 25ml suction pipes, add 15ml DC-CM to each culture bottle；With 10ml or 25ml suction pipes, 10ml is added to be resuspended
Sample (1.75 × 107/ ml) each culture bottle is arrived, it is tamping with lid；Culture bottle is shaken up, liquid is made to be paved with entire bottom of bottle；
Culture bottle be put into incubator (37 DEG C, 5%CO2；± 10 DEG C, ± 0.5%CO2), 2 hours 30min ±, make cell adherent；
IMDM be put into incubator (37 DEG C, 5%CO2；± 10 DEG C, ± 0.5%CO2), rinse culture bottle 2 times with 35ml IMDM；It needs
IMDM volumes=culture bottle quantity × 70ml IMDM；It rinses after culture bottle, adds the DC-CM of 50ml cell factors：It needs
IMDM=culture bottles quantity × 50ml；The concentration that IL-4 and GM-CSF is added all is 1000IU/ml；IL-4 is diluted, 1%HAS is used
To 1000IU/ml inside PBS；5-10 culture bottle of operation is to reduce the time being exposed in air every time；Culture bottle from
It is taken out in incubator, jiggles culture bottle；Blow adherent cell off with 2ml suction pipes；35ml temperature IMDM to each culture bottle,
Pay attention to：Add from the acellular side of bottle wall.A loose lower bottle cap, gently precious jade culture bottle, makes still adherent cell get off.Gently precious jade
Culture bottle avoids cell from being attached on wall.It is laid flat culture bottle.With 2ml suction pipes, IMDM is shifted, pays attention to tilting culture bottle.Use 35ml
IMDM is rinsed once again.Add the DC-CM that 50ml contains cell factor to each culture bottle, capping.It is gently laid flat culture bottle, is made
Liquid covers bottom of bottle.Culture 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 culture bottle quantity is less than 50,50 are prepared
The cell factor of a culture 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 culture bottle.
Liquid in mixing culture bottle (after cell factor is added).Culture 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 culture bottle quantity X30ml+300ml=needs；By culture 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 culture 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.Culture 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, is used in combination 25ml PPM that cell is resuspended, and the harvest pipe DC cells of harvest and flush pipe DC cells are merged
Enter same pipe, indicates：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, a concentration of 5ug/ml.Pine lid after be put into incubator (37 DEG C, 5%CO2；±10
DEG C, ± 0.5%CO2), incubator, mixing, 1.5 hours total times are taken out per 30min.The DC cells for taking 0.2ml 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.Wherein, Xg is relative centrifugal force.
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 1-34.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 XXX, female, 68 years old.Adenocarcinoma of lung, clinical IV phases, lung tumors interventional treatment 1 time, gemcitabine combination with cisplatin
It is in progress after chemotherapy 6 times, the molecular targeted medicine drug resistances of EGFR.The multiple transfer of intrapulmonary, hepatic metastases, pleura metastasis, Bone tumour, Intraperitoneal lymph
It carries down shifting.Pulmonary lesions tissue biopsy is taken, 488 tumor development related gene Panel and HLA typing chip detections are carried out
Afterwards, patient carries EGFR 19DEL and is mutated patient, and HLA partings are HLA-A：A*1001 A*3101；HLA-B:B*3501 B*
4007；HLA-C：C*0403 C*0801；HLA-DQB1：DQB1*0301 DQB1*0302；HLA-DRB1：DRB1*0405
DRB1*1502。
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 before and after group (hereinafter referred to as " medication "), and pass through iconography
Tumor size variation in 6 weeks before and after observation medication, as a result as depicted in figs. 1 and 2.Specific peptide chain selection is as follows：SEQ ID
No：3+SEQ ID No：11+SEQ ID No：15+SEQ ID No：18+SEQ ID No：19+SEQ ID No：21+SEQ ID
No：33.
Fig. 1 is HLA*A3101-HVKITDFGR Tetramer colored graphs, wherein Fig. 1-A are colored graph before medication, CD8
+ Tetramer+T a concentration of 2.7%；Fig. 1-B are 3 weeks after stain chromatic graphs of medication, CD8+Tetramer+T a concentration of 3.4%；Fig. 1-C
For 6 weeks after stain chromatic graphs of medication, CD8+Tetramer+T a concentration of 4.8%；As can be seen that amount of speckle has obviously 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 is lung tumors CT figure before and after medication, and wherein Fig. 2-A are that CT schemes before medication, mediastinum tumor area be 4cm ×
5cm；Fig. 2-B are that CT schemes after medication 6 weeks, it can be seen that tumor regression to 2cm × 3cm, front and back variation are 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 XXX, female, 72 years old, left adenocarcinoma of lung, after 6 periods of chemotherapy, the swollen object I125 seeds implanted of left lung was postoperative, takes orally
It is in progress after molecular targeted medicine Gefitinib.The left multiple transfer of intrapulmonary, right lung transfer.Right lung tumor aspiration biopsy is carried out, carries out 488
After a tumor development related gene Panel and HLA typing chip detection, patient carries EGFR 19DEL mutation.HLA
Parting is HLA-A：A*0301 A*3103；HLA-B:B*1601 B*4003；HLA-C：C*0702 C*0601:；HLA-DQB1：
DQB1*0201 DQB1*0301；HLA-DRB1：DRB1*0501 DRB2*1104.
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：9+SEQ ID No：14+SEQ ID No：17+SEQ ID No：23+SEQ ID No：28+
SEQ ID No：34.
Pretherapy and post-treatment lung tumors size variation situation is as shown in figure 3, as seen from Figure 3, before medication treatment, left lung neoplasm is big
Small 2cm × 3cm (Fig. 3-A)；7 weeks after medication treatment, left lung neoplasm disappears (Fig. 3-B) substantially, 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 the blastomogenic Dendritic Cells of production, it is in as antigen
Antigenic information can be presented to T cell by the Dendritic Cells of delivery cell, be interacted with T cell, so that T cell is generated specificity and killed
Hinder tumour cell, plays the role of killing tumor cell, and with obvious effects.
Embodiment 3-60
Embodiment 3-60 takes variety classes, different degrees of cancer patient to carry out 488 tumor development related genes
After the detection of Panel and HLA typing chips, patient is to carry EGFR 19DEL mutation patients, uses different Antigenic Peptides respectively
The combining form of chain group is treated, once a week, totally 12 weeks.HLA*A3101-HVKITDFGR of embodiment 3-60
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 1-60, 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 (after carrying out the detection of 488 tumor development related gene Panel and HLA typing chips,
Patient is to carry EGFR 19DEL mutation patient) treat during, before detecting medication with ELISA, medication 3 weeks, 7 weeks, 11
The specific IFN-γ secretion situation in week, concrete outcome is as shown in table 1, and dosage is identical as embodiment 1-60；Wherein, comparative example
1-5 is added without peptide chain.
As it can be seen from table 1 embodiment 1-60,11 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 1-60, 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 1-60 further demonstrates the effect of the present invention.
Table 1IFN- γ secretion statistics lists
Then, the rate of side effects of embodiment 1-60 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.
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 1-34.
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 34 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.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810184638.3A CN108409832A (en) | 2018-03-07 | 2018-03-07 | A kind of Antigenic Peptide chain group for treating tumour and its application in drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810184638.3A CN108409832A (en) | 2018-03-07 | 2018-03-07 | A kind of Antigenic Peptide chain group for treating tumour and its application in drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108409832A true CN108409832A (en) | 2018-08-17 |
Family
ID=63129987
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810184638.3A Withdrawn CN108409832A (en) | 2018-03-07 | 2018-03-07 | A kind of Antigenic Peptide chain group for treating tumour and its application in drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108409832A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101208354A (en) * | 2005-02-24 | 2008-06-25 | 安姆根有限公司 | Epidermal growth factor receptor mutations |
| 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 |
-
2018
- 2018-03-07 CN CN201810184638.3A patent/CN108409832A/en not_active Withdrawn
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101208354A (en) * | 2005-02-24 | 2008-06-25 | 安姆根有限公司 | Epidermal growth factor receptor mutations |
| 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)
| 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》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4987698B2 (en) | Cancer-related antigen analog peptide and use thereof | |
| CN104262459B (en) | Acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide, and vaccine and pharmaceutical application of acute monocytic leukemia-associated antigen MLAA-34 epitope polypeptide | |
| CN108250269A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| CN110812496B (en) | Rapid drug sensitivity detection method for antitumor drug | |
| CN108440646A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| CN108484776B (en) | A kind of fusion protein, preparation method and applications | |
| JPWO2007043630A1 (en) | NKT cell stimulant administered submucosally in upper airway | |
| CN108440647A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| CN105125576B (en) | A kind of pharmaceutical composition for treating cancer | |
| CN108250268A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| EA015510B1 (en) | Method for enhancing the amount of mononuclear cells in a subject suffering from cancer, and pharmaceutical combination used therefor | |
| CN106222141A (en) | NK cell culture fluid and cell culture processes | |
| CN108218961A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| CN108047308A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| Xu et al. | Carbohydrate-based adjuvants activate tumor-specific Th1 and CD8+ T-cell responses and reduce the immunosuppressive activity of MDSCs | |
| US20220313804A1 (en) | Hla tumor antigen peptides of class i and ii for treating mammary/breast carcinomas | |
| CN108484731A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| CN108218959A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| BR112020008668A2 (en) | nanoparticles containing synthetic gm3 ganglioside variants as adjuvants in vaccines | |
| CN108409832A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| CN113416240A (en) | Universal antigen peptide library and kit for inducing tumor specific immune response | |
| CN108218960A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| Li et al. | Whole tumor cell vaccine with irradiated S180 cells as adjuvant | |
| CN108440648A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug | |
| CN108047309A (en) | A kind of Antigenic Peptide chain group for treating tumour and its application in drug |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180817 |