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Effect of monoclonal antibody 17‐1A and gm‐CSF in patients with advanced colorectal carcinoma—long‐lasting, complete remissions can be induced
Author(s) -
Ragnhammar Peter,
Fagerberg Jan,
Frödin JanErik,
Hjelm AnnaLena,
Lindemalm Christina,
Magnusson Inger,
Masucci Giuseppe,
Mellstedt Håkan
Publication year - 1993
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/ijc.2910530508
Subject(s) - monoclonal antibody , antibody dependent cell mediated cytotoxicity , medicine , effector , immunology , granulocyte macrophage colony stimulating factor , antibody , granulocyte , colorectal cancer , cancer research , gastroenterology , cytokine , cancer
Antibody‐dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of unconjugated monoclonal antibodies (MAbs) in tumor therapy. The antitumor activity of MAbs might therefore be augmented if the cytotoxic capability of the effector cells could be increased. In an in vitro system, the killing capacity of MAb was significantly enhanced by pre‐treatment of the effector cells with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Based on these findings, the therapeutic effect of the combination of mouse MAb 17‐IA (IgG 2a ) and GM‐CSF was evaluated in 20 patients with metastatic colorectal carcinoma (CRC). The patients received GM‐CSF for 10 days and a single i.v. infusion of MAb 17‐IA on day 3 of the cycle. Four cycles were given at 1‐monthly intervals. There was a continuous increase in blood monocytes and lymphocytes during all 4 GM‐CSF cycles. Neutrophils and eosinophils were also significantly augmented but in a biphasic manner and the cell counts on day 10 of cycle IV were significantly lower than in cycles I and II. GM‐CSF‐related side‐effects were of no major clinical importance. During the third cycle, an immediate‐type allergic reaction (ITAR) against MAb 17‐ IA occurred in most patients, necessitating reduction of the MAb dose as well as of the infusion rate. Two patients achieved complete remission. One patient had a minor response, and 3 other patients were considered to have stable disease >3 months.