CN103417956A - Application of feedback CIK cell and interleukin-2 in mild moderate dose to combined and sequenced chemotherapy for treating later period non-small cell lung cancer - Google Patents
Application of feedback CIK cell and interleukin-2 in mild moderate dose to combined and sequenced chemotherapy for treating later period non-small cell lung cancer Download PDFInfo
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- CN103417956A CN103417956A CN2013103085990A CN201310308599A CN103417956A CN 103417956 A CN103417956 A CN 103417956A CN 2013103085990 A CN2013103085990 A CN 2013103085990A CN 201310308599 A CN201310308599 A CN 201310308599A CN 103417956 A CN103417956 A CN 103417956A
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Abstract
The invention belongs to the technical field of medical drugs, and discloses an application of feedback CIK cell and interleukin-2 in mild moderate dose to combined and sequenced chemotherapy for treating later period non-small cell lung cancer. Peripheral venous blood of a patient is drawn, cultivation, amplification and activation of a CIK cell are performed, feedback of CIK is performed while infusing IL-2, so that cancer cells can be effectively killed, the immunity of an organism is enhanced, and the excellent antineoplastic function is realized, the application of feedback CIK cell and interleukin-2 in mild moderate dose to combined and sequenced chemotherapy for treating later period non-small cell lung cancer is realized based on plenty of application through clinical tests.
Description
Technical field
The invention belongs to medical technical field, relate to the CIK cell and feed back with the median dose interleukin-2 application that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung.
Background technology
Tumor be body under the effect of various tumorigenesis factor, body's immunity reduces, the cellular abnormality hypertrophy of local organization and the neoplasm that forms, the M & M of tumor increases year by year.Pulmonary carcinoma is the highest cancer of world today's sickness rate, and its morbidity number and death toll all occupy first of common cancer, and people's life and health in serious threat.In recent years, the chemotherapeutics for the treatment of pulmonary carcinoma is a lot, can kill most cancerous cell to a certain extent, but because it has existence and the low inferior factor of late tumor patient immunity of organisms of serious toxicity, mdr cell, tumor stem cell and anti-radiation cell, cause enforcement and the therapeutic effect of therapeutic scheme to be subject to great impact, be difficult to all the time have breakthrough.
Development along with tumor immunology, Protocols in Molecular Biology, the Biotherapeutics of tumor starts to become the 4th kind of tumor treatment model after operation, radiation and chemotherapy, wherein, cytokine induced kill cell (CIK-Cytokine Induced Killer) adoptive immunotherapy has become developing direction important in tumor biotherapy.
Summary of the invention
Technical problem to be solved by this invention is for the deficiencies in the prior art described above, provides a kind of CIK cell to feed back with the median dose interleukin-2 application that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung.
For solving the problems of the technologies described above, the technical solution used in the present invention is: the CIK cell feeds back with the median dose interleukin-2 application that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung.
During application, first take out peripheric venous blood 40-50mL, the amplification of row CIK cell culture activates (10-16d), blood drawing begin column TP scheme chemotherapy (PTX135-175mg/m on the rear same day
2D1, DDP20mg/m
2D2-6), feed back the CIK continuous 5d of infusion IL-2 2,000,000 U simultaneously, every 3 weeks 1 courses for the treatment of, carry out altogether 4 courses for the treatment of.
The present invention adopts technique scheme to feed back with the median dose interleukin-2 application that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung by the CIK cell, because the CIK cell is externally to get peripheral blood mononuclear cells jointly to induce a group obtained to take CD3+CD8+CTL and CD3+CD56 through cytokine profiles be main foreign cell group, the powerful anti-tumor activity with the T lymphocyte, and the inside and outside competence for added value is strong, that a class is killed tumor activity more by force and killed the wider new antitumoral effector lymphocyte of tumor spectrum, this cell feeds back the associating Sequential Chemotherapy with the median dose interleukin-2 and controls advanced Non-small cell lung, by feeding back the CIK cell in body, can be under the prerequisite of not damaging the body immune system 26S Proteasome Structure and Function, the direct killing tumor cell, and the immunologic function of enhancing body, there is good antitumor action, the CIK cell is fast with its growth rate, kill tumor activity high, kill the tumor spectrum wide, the advantages such as side effect is little are considered to the preferred option of adoptive immunotherapy of new generation.
The specific embodiment
CIK cell of the present invention, be to get peripheral blood in patients 40-50mL, separates and obtain mononuclearcell, and these cells are joined and contain IFN-γ 1X10
6In the culture bottle of the complete culture solution of U/L, in 37 ℃, 5%CO
2Under condition, cultivate.Adding final concentration after cultivation 24h is 100 μ g/L mouse anti human CD3 monoclonal antibodies, 1X10
6U/L IL-2 and 1X10
6U/L IL-1 α continues to cultivate; Every day, the observation of cell growing state, changed liquid once every 2-3d, adds freshly in the IL-2 complete culture solution, cultivates the 10d left and right, after testing without after any pollution, and collection CIK cell 1.0 X10
10-1.3X10
10.
CIK cell of the present invention feeds back with the median dose interleukin-2 embodiment 1 that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung, first take out detection in peripheral blood of patients underwent 40mL, the amplification of row CIK cell culture activates 10d, blood drawing begin column TP scheme chemotherapy (PTX135-175mg/m on the rear same day
2D1, DDP20mg/m
2D2-6), feed back the CIK continuous 5d of infusion IL-2 2,000,000 U simultaneously, every 3 weeks 1 courses for the treatment of, carry out altogether 4 courses for the treatment of.
CIK cell of the present invention feeds back with the median dose interleukin-2 embodiment 2 that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung, first take out detection in peripheral blood of patients underwent 50mL, the amplification of row CIK cell culture activates 16d, blood drawing begin column TP scheme chemotherapy (PTX135-175mg/m on the rear same day
2D1, DDP20mg/m
2D2-6), feed back the CIK continuous 5d of infusion IL-2 2,000,000 U simultaneously, every 3 weeks 1 courses for the treatment of, carry out altogether 4 courses for the treatment of.
CIK cell of the present invention feeds back with the median dose interleukin-2 embodiment 3 that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung, first take out detection in peripheral blood of patients underwent 45mL, the amplification of row CIK cell culture activates 13d, blood drawing begin column TP scheme chemotherapy (PTX135-175mg/m on the rear same day
2D1, DDP20mg/m
2D2-6), feed back the CIK continuous 5d of infusion IL-2 2,000,000 U simultaneously, every 3 weeks 1 courses for the treatment of, carry out altogether 4 courses for the treatment of.
CIK cell of the present invention feeds back with the median dose interleukin-2 embodiment 4 that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung, first take out detection in peripheral blood of patients underwent 43mL, the amplification of row CIK cell culture activates 15d, blood drawing begin column TP scheme chemotherapy (PTX135-175mg/m on the rear same day
2D1, DDP20mg/m
2D2-6), feed back the CIK continuous 5d of infusion IL-2 2,000,000 U simultaneously, every 3 weeks 1 courses for the treatment of, carry out altogether 4 courses for the treatment of.
CIK cell of the present invention feeds back with the median dose interleukin-2 embodiment 5 that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung, first take out detection in peripheral blood of patients underwent 48mL, the amplification of row CIK cell culture activates 12d, blood drawing begin column TP scheme chemotherapy (PTX135-175mg/m on the rear same day
2D1, DDP20mg/m
2D2-6), feed back the CIK continuous 5d of infusion IL-2 2,000,000 U simultaneously, every 3 weeks 1 courses for the treatment of, carry out altogether 4 courses for the treatment of.
Clinical data
Physical data: from May, 2005-2009, accept altogether 105 routine patients year May for medical treatment, all through B ultrasonic, x-ray, CT and process histology and/or cytology, turn out to be III b or IV phase nonsmall-cell lung cancer (NSCLC), male 79 examples wherein, female's 26 examples, in age 25-78 year, all have measurable clinical foci, do not accept in the past other chemotherapy and radiations, KPS >=60 minute, the check result normals such as routine blood test, hepatic and renal function, electrocardiogram, estimate that life cycle was over 3 months.Get rid of and to suffer from cardiac insufficiency, hepatic and kidney function obstacle etc. and to have the mental illness can not cooperation person.Principle by random contrast is divided into treatment group and matched group, treatment group 52 examples, adopting property of employing CIK cell feeds back associating TP scheme chemotherapy with IL-2: first take out the capable CIK cell culture amplification of peripheric venous blood 40-50mL and activate (10-16d), blood drawing begin column TP scheme chemotherapy (PTX135-175mg/m on the rear same day
2D1, DDP20mg/m
2D2-6), feed back the CIK continuous 5d of infusion IL-2 2,000,000 U simultaneously, every three courses for the treatment of Monday, carry out altogether four courses for the treatment of.Matched group 53 examples, the simple TP scheme chemotherapy of row, chemotherapy regimen is identical with treatment group, every three courses for the treatment of Monday, totally four courses for the treatment of.
Observational technique
Observe short term effect, life quality, toxic reaction, Progression free survival phase and overall survival index.
Criterion of therapeutical effect
Therapeutic evaluation is according to the RESIST operative norm, and before treating, after treatment, CT and B ultrasonic are relatively.Alleviating (CR), partial rcsponse (PR), stable (SD) fully, progress (PD) is carried out therapeutic evaluation.The summation that disease control rate (DCR) is (CR+PR+SD), remission rate is RR(CR+PR).Life quality compares by the KPS scoring, and after treating, more than 10 minutes or 10 minutes, for improving, descending more than 10 minutes or 10 minutes is to worsen in raising, and raising or decline less than 10 are divided into stable, and total increase rate adds improvement for stablizing.
Efficacy result
1. curative effect is relatively: the disease control rate for the treatment of group and matched group be respectively 90.39% and 69.81%(P<0.01) remission rate be respectively 51.92% and 43.4%(P>0.05), be shown in Table 1.
Table 1: two groups of patient's curative effects compare [example (%)]
| Group | n | CR | PR | SD | PD | RR | DCR |
| Treatment group | 52 | 3(5.77) | 24(46.15) | 20(38.46) | 5(9.62) | 27(51.92) | 47(90.39) |
| Matched group | 53 | 2(3.77) | 21(39.62) | 14(26.42) | 16(30.19) | 23(43.4) | 37(69.81) |
2.KPS scoring improvement situation is relatively: treatment group KPS scoring improves, stable, worsen and be respectively 37,10,5 examples, matched group is respectively 30,5,18 examples, KPS scoring increase rate be respectively 90.39% and 66.04%(P<0.01).
3. untoward reaction relatively: in treatment group infusion CIK cell and IL-2 process, only have 4 examples heating to occur, body temperature is less than 38.5 ℃, recovers normal in anti symptom treatment 10h; 2 routine low grade fever are also arranged in matched group Chemotherapy in Patients process.Two groups of untoward reaction roughly the same, untoward reaction a situation arises zero difference.
4. overall survival (OS) and Progression free survival phase (PFS) are relatively: 1 year OS for the treatment of group and matched group is respectively 65.38%(34/52), 39.63%(21/53) (P<0.01), within 2 years, OS is respectively 38.46%(20/52), 16.98%(9/53) (P<0.05).1 year PFS for the treatment of group and matched group is respectively 46.15%(24/52), 24.53%(13/53) (P<0.05), within 2 years, PFS is respectively 21.15%(11/52), 5.66%(3/53) (P<0.05).
The present invention, by autologous CIK cellular immunization therapy, separates mononuclearcell from patient's human peripheral blood, after a large amount of amplifications, feeds back in body in vitro again, to improve rapidly body T cellular immune function, kills and wounds the tumor cell in patient body.The present invention uses autologous CIK cell and IL-2 to feed back associating PTX and DDP treats the effect that advanced NSCLC has obtained highly significant, there is obvious short term effect can improve its prognosis for advanced Non-small cell lung, make to obtain life cycle of patients with lung cancer significant prolongation.
Claims (1)
1. a CIK cell feeds back with the median dose interleukin-2 application that the associating Sequential Chemotherapy is controlled advanced Non-small cell lung.
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|---|---|---|---|
| CN2013103085990A CN103417956A (en) | 2013-07-23 | 2013-07-23 | Application of feedback CIK cell and interleukin-2 in mild moderate dose to combined and sequenced chemotherapy for treating later period non-small cell lung cancer |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109891238A (en) * | 2016-10-25 | 2019-06-14 | 生物技术Rna制药有限公司 | The dosage of immunotherapeutic agent determines |
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2013
- 2013-07-23 CN CN2013103085990A patent/CN103417956A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 尹先哲等: "CIK 细胞与白介素-2 回输联合同步化疗治疗晚期非小细胞肺癌临床研究", 《山东医药》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109891238A (en) * | 2016-10-25 | 2019-06-14 | 生物技术Rna制药有限公司 | The dosage of immunotherapeutic agent determines |
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Application publication date: 20131204 |