This study investigated the efficacy of cord blood-derived cytokine-induced killer (CB-CIK) biotherapy combined with second-line chemotherapy in treating advanced solid malignancies after first-line chemotherapy failure. Forty patients with advanced solid malignancies after first-line chemotherapy failure were divided into two groups: CB-CIK cells transfusion plus second-line chemotherapy (CB-CIK+Chemotherapy) group and second-line chemotherapy alone (Chemotherapy) group. The ORR and DCR were 30% and 80% in CB-CIK + Chemotherapy group compared with 15% and 70% in Chemotherapy group (P = 0.451 for ORR and P = 0.716 for DCR) respectively. The time to progression and the median survival time were 3.45 months (95% CI 2.30-4.60 months) and 11.17 months (95% CI 9.05-13.28 months) in CB-CIK+Chemotherapy group compared with 2.03 months (95% CI 1.23-2.82 months) and 7.52 months (95% CI 5.97-9.06 months) in Chemotherapy group respectively. Compared with patients in Chemotherapy group, the patients in CB-CIK+Chemotherapy group had significantly longer PFS (P = 0.031) and overall survival (P = 0.048). In vitro studies further revealed that CB-CIK cells could overcome drug resistance in cisplatin-resistant lung adenocarcinoma cell line A549/CDDP through downregulating ABCG-2 and P-gp and induce cytotoxicity through the high level expression of CD3, CD56, FasL, and CD69. This could explain why CB-CIK could have synergistic effects with second-line chemotherapy shown in this clinical study. We concluded CB-CIK cells combined with second-line chemotherapy can significantly improve PFS and median survival compared with second-line chemotherapy alone in patients with advanced solid malignancies after first-line chemotherapy failure.
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