Combination therapy with dendritic cell-based vaccine and chemotherapy is active against acute myeloid leukemia in a mouse model

Abstract

Acute myeloid leukemia (AML) is a malignant disorder of progenitor cells in myeloid hematopoiesis. The majority of AML patients achieve complete remission with the current therapeutic treatment but relapse frequently occurs which shortens survival of AML patients. The dismal cure rate of current therapeutic strategies stresses the urgent need of novel strategy to prevent relapse and lengthen the survival of AML patients. Therefore, DC based cancer immunotherapy presents as an attractive adjunct for the treatment of AML. We hypothesized that AML dendritic cell (DC)-based vaccine plus chemotherapy using cytosine arabinoside (AraC) induces better antitumor effect in AML mouse model. Therapeutic efficacy of syngeneic DC-based vaccine alone or in combination with chemotherapy in antitumor immunity was evaluated in vivo. Female C57BL/6 mice were challenged subcutaneously with murine C1498 AML cells and tumor bearing mice were treated as follows: 1) PBS injection; 2) cytosine arabinoside (AraC, 100 mg/kg) alone; 3) DC vaccine (2.0×106 cells/mouse) alone; 4) combination of AraC followed by DC vaccine (AraC-DC) treatment; and 5) DC vaccine followed by AraC and repeat DC injection (DC-AraC-DC). We found that individual treatments (DC vaccine or AraC treatment alone) induced only transient tumor regression with minimal survival advantage as compared to PBS control. The combinatorial therapy, both AraC-DC (P = 0.093) and DC-AraC-DC (P < 0.001) treatment, conferred greater tumor suppression effects and strongly prolonged median survival time of AML bearing mice (median survival 15 days & 20 days vs 10 days, respectively). The DC-AraC-DC treatment approach appears to be superior in increasing the tumor eradication as compared to AraC-DC treatment (P < 0.05). These findings raise the possibility of utilizing this approach to treat AML patients clinically.