The Clinical Research For Adoptive Immunotherapy Of Cytokine-induced Killer Cells On Patients With Malignant Solid Tumors

Objective: In recent years, cytokine-induced killer cells(CIK cells), one of the tumor biological therapeutics, has achieved good clincial outcomes with the strong anti-tumor activity, low toxicity and a broad tumor-killing spectrum. Studies have shown that a large number of autologous CIK cells infusion can remove residual tumor cells and small metastases of surgery, radiotherapy and chemotherapy in vivo, prevent recurrence and metastasis, and can improve the immune function of patient, quality of life and survival.This research investigate the effect of the adoptive immunotherapy of autologous CIK cells on the cellular immune function and quality of life of patients with maligant solid tumor, and evaluate efficacy and toxicity.Methods: The 58 cases of malignant tumor patients (including 24 patients without clear lesions and 34 patients with tumor lesions) accepted adoptive immunotherapy of autologous CIK cells. The changes of pre-treatment and post-treatment in patients with CD3~+, CD3~+ CD4~+, CD3~+ CD8~+, CD3~+CD56~+T lymphocyte subsets levels were detected by flow cytometry. Then it was compared with the T lymphocyte subsets levels of 12 healthy volunteers. The quality of life in pre-treatment and post-treatment patients was measured by EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30). The tumor size and tumor markers alleosis of patients with tumor lesions were measured by imageology and laboratory examination, and the toxicity of all patients was monitored.Results: 1, The 58 patients received adoptive immunotherapy of autologous CIK cells, compared with pre-treatment of autologous CIK cells, in peripheral blood, CD3~+, CD3~+ CD4~+ and CD3~+ CD56~+ T lymphocytes expression percentage rise were up-regulated significantly, the comparison has significant difference (P <0.05), while the CD3~+CD8~+cells increase was not obvious. Analysis stratified according to tumor load(24 patients without tumor lesions and 34 patients with tumor lesions), we found that before treatment, patients without tumor lesions, CD3~+, CD3~+CD56~+Tcell levels lower than the healthy group (P <0.05), but Post-treatment, compared with the healthy group, the level of T cell subsets had no significant difference; the self-control before and after treatment showed that compared with pre-treatment, CD3~+, CD3~+CD4~+, CD3~+CD56~+T cell expression percentage rise, CD3~+ CD8~+ cell expression percentage decline, only the level of CD3~+CD4~+cell changed significantly(P<0.05). Before treatment, patients with tumor lesions, CD3~+, CD3~+ CD4~+, CD3~+CD8~+, CD3~+CD56~+T cells were significantly lower than that of the healthy group, and there was significant difference (P <0.05), after treatment, the T cell subsets levels increased slightly, but only CD3~+, CD3~+CD56~+T cell level was still lower than that of the healthy group (P <0.05); the self-control before and after treatment showed that CD3~+, CD3~+ CD8~+, CD3~+ CD56~+ T lymphocytes expression percentage rise significantly (P <0.05). 2, The 58 patients, Karnofsky score and weight increased significantly than before, physical enhancement. EORTC QLQ-C30 scale evaluation quality of life improvement of 58 patients. In the functional scale, compared with pre-treatment, physical function and global quality of life scores were increased (P <0.05), while in the symptom scale, compared with pre-treatment, shortness of breath, pain, fatigue, sleeping disturbance, loss of appetite, nausea and vomiting scores were decreased obviously (P <0.05). Stratified analysis according to tumor load showed, patients without tumor lesions, in the functional scale, compared with pre-treatment, only role functioning was improved significantly (P <0.05), in the symptom scale, sleeping disturbance, loss of appetite and constipation were improved significantly (P <0.05); patients with tumor lesions, compared with pre-treatment, in the functional scale, physical function, cognitive function and global quality of life scores were increased obviously (P <0.05). While in the symptom scale, fatigue, nausea and vomiting, pain, shortness of breath, sleeping disturbance and loss of appetite scores were decreased(P <0.05). 3, Therapeutic evaluation of 34 patients with tumor lesions, including 1 patient showed a partial response, 27 patients showed a stable disease, 6 patients showed a progressive disease, but no case complete response, the clinical benefit rate was 82.35%; Dynamic monitoring tumor markers for this group of patients before and after treatment, only some of whom the level of tumor markers was stable, while the majority of patients of tumor markers had no obvious effect. 4, During treatment, there were 13 patients have fever in lower level. Laboratory examination showed that in adoptive immunotherapy of autologous CIK cells, compared with pre-treatment, routine blood test, clotting time, liver function, renal function and electrocardiogram were no obviously changes, and didn't appear other adverse reactions.Conclusion: 1, Adoptive immunotherapy of autologous CIK cells can significantly corrected disordered state of peripheral blood T cell subsets with malignant solid tumors, in order to improve cellular immune function, which is particularly evident in patients with tumor lesions; 2, Adoptive immunotherapy of autologous CIK cells can relieve some clinical symptoms, including shortness of breath, pain, nausea/vomiting, fatigue, sleeping disturbance, loss of appetite and so on. Meanwhile it can improve physical function, role function, cognitive function and global quality of life, and enhance patients health, improving quality of life and prolong survival. Patients with tumor lesions has more significant improvement in quality of life; 3, During short-term adoptive immunotherapy of autologous CIK cells, the majority of patients with advanced solid tumors remain stable disease, but the lesions of most patients lesions couldn't reduced at all after treatment, and the tumor markers was't significantly reduced, poor efficacy; 4, During adoptive immunotherapy of autologous CIK cells on patients with malignant solid tumors, the patients who have a fever, have no other significant side effects with effective and safe, low toxicity characteristics.