In vitro and in vivo antitumor effect of the anti-CD26 monoclonal antibody 1F7 on human CD30+ anaplastic large cell T-cell lymphoma Karpas 299.
CD26 is a M(r) 110,000 surface glycoprotein with diverse functional properties, including having a potentially significant role in tumor development, and antibodies to CD26 mediate pleomorphic cellular functions. In this report, we show that binding of soluble anti-CD26 monoclonal Ab 1F7 inhibits the growth of the human CD30+ anaplastic large cell T-cell lymphoma cell line Karpas 299 in both in vitro and in vivo experiments. In vitro experiments show that 1F7 induces cell cycle arrest at the G1-S checkpoint, associated with enhanced p21 expression that is dependent on de novo protein synthesis. Furthermore, experiments with a severe combined immunodeficient mouse tumor model demonstrate that 1F7 treatment significantly enhances survival of tumor-bearing mice by inhibiting tumor formation. Our data therefore suggest that anti-CD26 treatment may have potential clinical use for CD26+ hematological malignancies.
Ho
L
L
Department of Gastrointestinal Oncology, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Aytac
U
U
Stephens
L C
LC
Ohnuma
K
K
Mills
G B
GB
McKee
K S
KS
Neumann
C
C
LaPushin
R
R
Cabanillas
F
F
Abbruzzese
J L
JL
Morimoto
C
C
Dang
N H
NH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011506:Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000187:drug effects; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011506:Proteins; D018819:Dipeptidyl Peptidase 4