Premium
Synergistic cytotoxicity of iodine‐131‐anti‐CD20 monoclonal antibodies and chemotherapy for treatment of B‐cell lymphomas
Author(s) -
Johnson Timothy A.,
Press Oliver W.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000101)85:1<104::aid-ijc19>3.0.co;2-g
Subject(s) - cytotoxicity , monoclonal antibody , cd20 , chemotherapy , cancer research , medicine , antibody , iodine , lymphoma , monoclonal , b cell , immunology , pathology , chemistry , biochemistry , in vitro , organic chemistry
Preliminary clinical trials suggest that iodine‐131 ( 131 I)‐labeled anti‐CD20 monoclonal antibodies (MAbs) are effective single agents for the treatment of relapsed non‐Hodgkin's B‐cell lymphomas. However, despite high initial response rates, most patients treated in this manner will eventually relapse. We hypothesized that regimens combining 131 I‐anti‐CD20 antibodies with standard chemotherapeutic agents may provide synergistic anti‐tumor effects, and may improve the durability of responses in patients with lymphoma. To identify promising agents for clinical testing, we assessed the in vitro cytotoxicity of combinations of 131 I‐anti‐B1 (anti‐CD20) antibody and 8 chemotherapeutic agents using 2 human CD20‐expressing lymphoma cell lines and 2 corroborative assays, the thiazolyl tetrazolium bromide (MTT) and the Trypan blue dye exclusion assays. ID 50 isobolographic and dose modification factor (DMF) analyses were used to classify interactions between the 131 I‐anti‐B1 antibody and the chemotherapeutic agents as supra‐additive (synergistic), additive or sub‐additive. Cytarabine and fludarabine were markedly supra‐additive when combined with the radioimmunoconjugate, with the combination enhancing cytotoxicity 3.5‐ to 5.2‐fold over the level expected by simple addition of the 2 agents (DMFs 3.5–5.2). Etoposide, doxorubicin and SN‐38 were moderately supra‐additive (DMFs 2.0–2.8). Cisplatin and 4‐hydroxycyclophosphamide exhibited merely additive cytotoxicity (DMFs 1.0–1.1). Thus, combination regimens containing 131 I‐labeled anti‐CD20 antibodies and nucleoside analogs or topoisomerase inhibitors appear particularly attractive for future clinical trials. Int. J. Cancer 85:104–112, 2000. © 2000 Wiley‐Liss, Inc.