Open AccessSusceptibility of human T‐cell leukemia virus type I‐infected cells to humanized anti‐CD30 monoclonal antibodies in vitro and in vivo
Author(s) -
Maeda Naoyoshi,
Muta Hiromi,
Oflazoglu Ezogelin,
Yoshikai Yasunobu
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01354.x
Subject(s) - cd30 , in vivo , monoclonal antibody , t cell leukemia , medicine , in vitro , leukemia , cell culture , cell growth , cancer research , immunology , t cell , virology , antibody , biology , lymphoma , biochemistry , immune system , genetics , microbiology and biotechnology
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. ( Cancer Sci 2009)