In a study reported in Clinical Cancer Research, Gammaitoni and colleagues investigated the tumor-killing activity of cytokine-induced killer cells against autologous metastatic melanoma and putative cancer stem cells.
The investigators developed a preclinical autologous model using same patient-generated cytokine-induced killer cells and tumor targets to capture the unique biology of each patient/tumor pairing. A putative melanoma stem cell subset was visualized and immunophenotypically defined in primary tumor cell cultures using a novel gene-transfer strategy exploiting the ability of such cells to activate the promoter of stemness gene Oct4.
Cytokine-induced killer cells from 10 patients with metastatic melanoma were expanded, and primary tumor cell cultures established and characterized from the same patients were used as autologous targets. The patient-derived cytokine-induced killer cells efficiently killed autologous metastatic melanoma cells, with up to 71% specific killing.
In in vivo testing, the cells produced delayed tumor growth, increased necrotic areas, and lymphocyte infiltration at tumor sites in autologous metastatic melanoma. The metastatic melanoma cultures featured an average of 11.5% putative melanoma stem cells, as assessed by Oct4 promoter activity and expression of stemness markers (Oct4, ABCG2, ALDH, and MITF), with expression being confirmed on melanoma stem cell target molecules recognized by the cytokine-induced killer cells. Cytokine-induced killer cell killing activity against melanoma stem cells was up to 71%.
The investigators concluded, “For the first time, the intense killing activity of cytokine-induced killer cells against autologous metastatic melanoma, including [melanoma stem cells], has been shown. These findings move clinical investigation of a new immunotherapy for metastatic melanoma, including [melanoma stem cells], closer.” ■
Gammaitoni L, et al: Clin Cancer Res 19:4347-4358, 2013.