Susceptibility of human T-cell leukemia virus type I-infected cells to humanized anti-CD30 monoclonal antibodies in vitro and in vivo.

摘要

Adult T-cell leukemia (ATL) is an aggressive malignancy of activated CD4(+) T cells associated with human T-cell leukemia virus type I (HTLV-I) infection. No conventional chemotherapy regimen has appeared successful in patients with ATL, thus establishing effective therapy is urgently required. In some cases, ATL tumor cells express CD30 on the cell surface, therefore, a therapy with mAb against CD30 would be beneficial. To investigate the effect of CD30-mediated therapy on ATL, we assessed SGN-30, a chimeric anti-CD30 mAb, and SGN-35, a monomethyl auristatin E-conjugated anti-CD30 mAb, in vitro and in vivo. Three HTLV-I-infected cell lines were co-cultured with SGN-30 or SGN-35, and the growth-inhibitory effects on the HTLV-I-infected cells were evaluated using an in vitro cell proliferation assay and cell cycle analysis. SGN-30 and SGN-35 showed growth-inhibitory activity against the HTLV-I-infected cell lines by apoptosis and/or cell growth arrest in vitro. To further investigate the effects of SGN-30 and SGN-35 on HTLV-I-infected cells in vivo, we used NOD/SCID mice subcutaneously engrafted with HTLV-I-infected cells. Both mAbs significantly inhibited the growth of HTLV-I-infected cell tumors in the NOD/SCID murine xenograft models. These data suggest that CD30-mediated therapy with SGN-30 or SGN-35 would be useful for patients with ATL.