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

Granulocyte/macrophage-colony-stimulating factor (GM-CSF) has previously be en indicated to enhance the therapeutic effect of the anti-colorectal carci noma mAbl7-1A as well as to augment in vivo immune effector functions. In v itro interleukin-2 (IL-2) augmented GM-CSF-induced antibody-dependent cellu lar cytotoxicity, a mechanism considered to be of significance for the ther apeutic effect of mAb. A treatment regimen was elaborated that combined mAb l7-1A (400 mg at day 3 of a 10-day treatment cycle) with the simultaneous a dministration of GM-CSF (250 mu mg/m(2) once daily) and IL-2 (2.4 x 10(6) U /m(2) twice daily) for 10 days. The treatment cycle was repeated once a mon th. Twenty patients with advanced colorectal carcinoma were included in the study. One patient obtained a partial remission and 2 patients stable dise ase for 7 and 4 months respectively. The median survival time from the star t of mAb therapy was 8 months. Owing to allergic reactions, the planned mAb l7-1A 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 be-cause of side-effects. The subjective tolerabilit y of the treatment was considered good or acceptable in more than 80% of th e patients. The increment in white blood cell subsets induced by the cytoki nes decreased by increasing number of courses. This particular regimen did not augment the therapeutic effect of mAbl7-1A anticipated from in vitro da ta 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 suppre ssion in vivo resulting from an impaired human anti-(mouse Ab) and anti-idi otypic antibody response as well as antibody-dependent cellular cytotoxicit y, on the basis of a comparison of mAbl7-1A/GM-CSF/IL-2- and mAb17-1A/GM-CS F-treated patients.