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The Study of Clinical Application of Cytokine-Induced Killer Cells on Renal Cell Carcinoma

Author: XiaoJunJuan
Tutor: LiYan
School: Shandong University
Course: Oncology
Keywords: Cytokine-induced killer cell IL-2 biological therapy renal cell carcinoma
CLC: R737.11
Type: Master's thesis
Year: 2011
Downloads: 105
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Abstract


Objective:Renal cell carcinoma(RCC), which incidence is only after bladder cancer in urinary malignant tumors, has very poor prognosis.In clinical,30%-40% renal cell carcinoma patients have distant metastasis during frist treatment, and about half patients have recurrence or metastasis after surgery. Because of its insensitivity to chemotherapy and radiotherapy and high recurrence rate of advanced renal cell carcinoma, it still lack of effective treatment, although surgical resection is the only effective treatment of localized renal cell carcinoma currently. Since its cell special biological characteristics make renal cell carcinoma becoming one of a few tumors which immunotherapy is effective to.With the rapid development of molecular biology and immunology disciplines, immunotherapy has become the fourth treatment of tumors after surgery, radiotherapy and chemotherapy. A new type immune cell,cytokine-induced killer cells(CIK), also referred to natural killer-like T cells,is a group of stromal cells expanded from human peripheral blood mononuclear cells stimulated with a series of cytokines (CD3McAb, IL-2, IFN-γ, IL-1α, etc.) in vitro, in which the CD3+CD56+T cell is predominant. CIK cells possess the advantages of strong proliferation, effective tumor-killing activity, broader antitumor spectrum, sensitivity to the multidrug-resistant tumor cells, killing GO phase cells,escaping from cyclosporine A (CsA),FK506 and other immunosuppressive agents, minimal toxicity to normal bone marrow hematopoietic precursor cells, and resistant to apoptosis induced by effector cells through Fas-FasL. Thus, CIK cells open up a new perspective for tumor immunotherapy.In this study, we selected thirty-four renal cell carcinoma patients of AJCC stageⅠ-Ⅲafter radical mastectomy. In the treatment group nineteen patients were treated with two-cycles’CIK with IL-2 simultaneously, and fifteen patients were only treated by IL-2 in the control group. We observed the general state of health、the variation of liver and kidney function and immune function before and after the treatment.Also, we obversed the adverse reactions in the course of treatment, and we evaluated one-year survival rate of the two groups and provided scientific bases for clinical bio-immunotherapy.Methods:1. Thirty-four renal cell carcinoma patients of AJCC stageⅠ-Ⅲ, were treated with IL-2 1-2 weeks after radical mastectomy. IL-2 was injected 200 million U/times, day 1-14, and 21 days for a course.2. The 34 patients were divided into treatment group and control group. The contrast between the two groups were not significantly different and the two groups are comparable. In the treatment group nineteen patients were treated with two-cycles’autologous peripheral blood CIK cells treatment CIK combined with IL-2, and fifteen patients were only treated by IL-2 in the control group.3. The phenotype and proliferation were observed dynamicly; In the course of treatment, we closely observed adverse reaction and general health state of patients. The level of T cell subsets (CD3+T cells, CD4+T cells, CD8+T cells, CD4+/CD8+ratio and CD4+CD25+ regulatory T cell) and NK cells were detected before and after the treatment. Also, we evaluated one-year survival rate of the two groups.Results:1. The number and volume of the cultured cells were significantly increased from day 4, the number up to largest from day 14, the number began to decline from day 16.2. In addition to one case there was no obvious change, the remaining eighteen in the treatment group had different levels ease, such as improving appetite and strength, alleviating cancer pain, gaining weight after two-cycle CIK treatment. Relatively in the control group three cases there were no obvious change. Compared with the control group, the treatment group was significantly higher Karnofky(KPS).3. There was no change of leukocyte、transaminase、creatinine、urea nitrogen before and after treatment in the two groups. In the course of treatment, we didn’t obversed any bone marrow suppression, liver or kidney failure, showing CIK treatment side effects on the other hand.4. In the CIK group, the level of CD8+T cell and CD4+CD25+ regulatory T cell decreased(p (0.05), meanwhile the CD3+T cell subsets、CD4+T cell subsets、CD4+/CD8+ ratio and NK cells significantly increased one month after CIK therapy(p (0.05).But in the control group, there was none significant change in the level of CD8+T cell and CD4+CD25+regulatory T cell (p〉0.05), and the increase of CD3+ T cell subsets、CD4+T cell subsets、CD4+/CD8+ ratio and NK cells was not significant〈p〉0.05).5. In the course of IL-2 treatment, three cases in the CIK group and two cases in the control group appeared fever, up to 38.3℃, lasting 4 to 6 hours, and only one patient needed treatment. During CIK reinfusion, only one case appeared fever, around 38℃, and other serious adverse reactions such as chills、allergy、shock、rash didn’t occur.6. We evaluated the one-year survival rate of the CIK and control groups,100% and 87% respectively, there was no significant difference between the two groups(p=0.10).Conclusions:After the treatment of CIK cells(two courses) combined with IL-2,renal cancer patients after surgery had obviously improved general state of health and the quality of life. And the imbalance of T cell subsets has been improved effectively, and the diseases has been controlled.In addition to fever there was no other significant adverse reaction. With high security, CIK therapy have good prospects in the clinical application and is worthy of further promotion.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Urinary tumors > Kidney,renal pelvis tumor
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