Clinical effects of monoclonal antibody 17-1A combined with granulocyte/macrophage-colony-stimulating factor and interleukin-2 for treatment of patients with advanced colorectal carcinoma |
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Authors: | A.-L. Hjelm Skog P. Ragnhammar J. Fagerberg J.-E. Frödin M. Goldinger H. Koldestam M. Liljefors B. Nilsson J. Shetye P. Wersäll H. Mellstedt |
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Affiliation: | Immune and Gene Therapy Laboratory, Cancer Centre Karolinska, Stockholm, Department of Oncology (Radiumhemmet), Karolinska Hospital, SE-171 76 Stockholm, Sweden Tel.: +46-8-517 743 08 Fax: +46-8-31 83 27, SE Department of Surgery, L?wenstr?mska Hospital, Upplands-V?sby, Sweden, SE
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Abstract: | Granulocyte/macrophage-colony-stimulating factor (GM-CSF) has previously been indicated to enhance the therapeutic effect of the anti-colorectal carcinoma mAb17-1A as well as to augment in vivo immune effector functions. In vitro interleukin-2 (IL-2) augmented GM-CSF-induced antibody-dependent cellular cytotoxicity, a mechanism considered to be of significance for the therapeutic effect of mAb. A treatment regimen was elaborated that combined mAb17-1A (400 mg at day 3 of a 10-day treatment cycle) with the simultaneous administration of GM-CSF (250 μmg/m2 once daily) and IL-2 (2.4 × 106 U/m2 twice daily) for 10 days. The treatment cycle was repeated once a month. Twenty patients with advanced colorectal carcinoma were included in the study. One patient obtained a partial remission and 2 patients stable disease for 7 and 4 months respectively. The median survival time from the start of mAb therapy was 8 months. Owing to allergic reactions, the planned mAb17-1A dose had to be reduced by repeated infusions. At the fourth treatment cycle only 25% received the planned mAb dose. In 3 patients the GM-CSF and IL-2 dose was reduced because of side-effects. The subjective tolerability of the treatment was considered good or acceptable in more than 80% of the patients. The increment in white blood cell subsets induced by the cytokines decreased by increasing number of courses. This particular regimen did not augment the therapeutic effect of mAb17-1A anticipated from in vitro data but rather hampered the clinical effect of the antibody. The reason for this is not clear but a possibility might be the induction of immune suppression in vivo resulting from an impaired human anti-(mouse Ab) and anti-idiotypic antibody response as well as antibody-dependent cellular cytotoxicity, on the basis of a comparison of mAb17-1A/GM-CSF/IL-2- and mAb17-1A/GM-CSF-treated patients. Received: 25 February 1999 / Accepted: 15 July 1999 |
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Keywords: | Colorectal carcinoma Monoclonal antibodies GM-CSF-IL-2 |
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