Efficacy And Safety Of Co-cultured Tumor Antigen-loaded Dendritic Cells And Cytokine-induced Killer Cells Combined With Routine Therapy In The Treatment Of Advanced Retinoblastoma

Objective To evaluate the clinical efficacy and safety of co-cultured autologous tumor antigen-loaded dendritic cells(DC) and cytokine-induced killer cells(CIK)(Ag-DC-CIK) combined with routine therapy(combined with chemotherapy, surgery) in the treatment of advanced retinoblastoma(RB).Methods 26 patients suffered with RB whom were diagnosed as advanced RB in the General Hospital of the Chinese People’s Armed Police Forces between January 2011 and January 2014. 13 patients received Ag-DC-CIK combined with routine treatment(combination group). The other patients accepted routine therapy(routine group). The study approved by the Ethics Committee. After the guardians of patients signed informed consent, 10-35 ml autologous peripheral blood were collected one day before chemotherapy and amplification in vitro 13-15 days. The prepared cells were infused once every other day, total of twice. The change of short-term outcome, immunologic function, the quality of life, adverse effects, and safety in each group were evaluated.Results The combination group totally received 67 cycles(134 times) Ag-DC-CIK therapy. The minimum therapies of treatments were two cycles, while the maximum were 10 cycles. Reinfusion of cells range from 5×109/L to 60×109/L(average: 27.30×109/L). Reinfusion of time range from 4 hours to 8.5 hours(average: 5.83 hours). All patients were followed up until December 2014. The follow-up time of combination group range from 4 months to 35 months(average: 23.31 months), and the routine group range from10 months to 39 months(average: 23.54 months). 3 cases of combination group died during follow-up, 4 cases of parents give up finally due to economic reasons, and the remaining 6 cases were followed up for survival. 3 cases of routine group died during follow-up, 5 cases give up treatment because of economic difficulties, and other cases were followed up for survival. At the end of the follow-up, all patients of combination group who suffered D got the opportunity of reserving eyes; 2 out of 4 patients who lost the opportunity to operation had surgery eventually. All the group D patients of routine group were enucleated. 1 out of 4 patients who lost the opportunity to operation had surgery eventually. The 1-year survival rate of combination group was 92.3%, while the routine group was 84.6%(p>0.05). CD3+, CD4+, CD4+ / CD8+ and CD3+CD56+ proportion of the combination group was higher than another group(p<0.05), CD8+ proportion of the combination group was lower than the routine group, and the difference was statistically significant(p<0.05). The mental status, activity, appetite and weight loss were improved after the combined treatment(p<0.05). The neutropenia, anemia, thrombocytopenia, nausea and vomiting of combination group were get better than the other group(p<0.05). Only one cases of patient had a fever during the therapy, and could return to normal itself. Other patients had normal vital signs during treatment. No patients had allergic reactions and organ dysfunction. Both groups of patients’ hepatorenal and kidney function, blood biochemical and ECG had no statistical differences(p>0.05).Conclusions Ag- DC-CIK combined with routine therapy in the treatment of advanced RB was efficient and safe. It not only had good security, but also can improve children’s short-term effect, immune function, reduce side effects of chemotherapy, enhancing tolerance to chemotherapy in children and improve the quality of life.