Immunomodulatory effect of DC/CIK combined with chemotherapy in multiple myeloma and the clinical efficacy

Before/After treatment

Before/After treatment

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Summary

This study investigates the efficacy of immunotherapy using dendritic cells (DCs) and cytokine-induced killer (CIK) combined with chemotherapy on patients with multiple myeloma. The results suggest that the treatment has good clinical efficacy and prospect for MM.

Patients characteristics

50 patients with histologically confirmed multiple myeloma (MM). all patients had good general conditions with expected survival longer of 3 months.

Methodology

DC and CIK cell preparation
PBMNCs in the amount of 1.0 to 5.0×1010 were collected in the combined therapy group and subjected to adherent culture at 37°C in a saturated 5% CO2 incubator. The suspended cells were removed, and the adherent cells were added with GM-CSF and IL -4 to induce DCs. Into the suspended cells, RPMI1640 medium containing IFN-γ and anti-CD3 monoclonal antibodies, IL-12 and IL-1 were added to induce CIK.
Mononuclear cells and DCs at 7 days of culture were added with 10 μL FITC-labeled CD83 and CD86 monoclonal anti- bodies and 10 μL PE-labeled HLAII monoclonal antibodies. A small amount of PBMNCs and CIK cells at 7 days of culture were harvested and added with 10 μL of FITC-labeled CD3, CD8 and CD56 monoclonal antibodies, respectively.

Treatment

The 24 cases in the simple chemotherapy group received BD chemotherapy consisting of bortezomib, during each cycle that lasted 28 days. 26 cases in the combined therapy group received DC/CIK adoptive immunotherapy.
DCs and CIK cells were subjected to 1:10 mixed culture at 7 days. These cells were transfused back at 15-20 days of chemotherapy for a total of 6 times and once daily. The amount of cells transfused each time 9 was 2.0-5.0×10 . Before each transfusion, the cells were centrifuged, washed, resuspended in 100 ml of normal saline and intravenously injected within 2 hours. All cases in the combined therapy group received immunotherapy for over 3 cycles.

Results

Adverse reaction
Five cases in the simple chemotherapy group reported the symptoms of nerve terminal injury such as mild numbness of the four limbs. Two cases in the combined therapy group reported transient chills and fever 2 h-3 h after blood cell transfusion. The highest body temperature reached 38.2°C, and the symptoms disappeared after symptomatic treatment and the symptoms did not recur. No cases died during the trial period.
Comparison of Tregs cell before and after treatment in the two groupsThe CD4+CD25+/CD4+ and CD4+CD25+FoxP3+/ CD4+CD25+ ratios in the peripheral blood in both groups decreased after 3 weeks of treatment (P<0.05). These two ratios in the combined therapy group were much lower than those of the simple chemotherapy group after treatment (P<0.05). The positive rate of NKG2D increased after treatment in both two groups (P<0.05), and the positive rate in the combined therapy group was significantly increased compared with that in the simple chemotherapy group.

Conclusion

These results indicated better immunomodulatory effect of the combined therapy. DC/CIK immunotherapy combined with chemotherapy has a good clinical efficacy and prospect for MM, reversing the Th1 to Th2 shift and increasing the anti-tumor capacity of the immune system.

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Scientific article publishing date 10/15/2015

Immucura identifier BSC21_252EN

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