THE THERAPEUTIC USE OF THE UNCONJUGATED MONOCLONAL-ANTIBODIES (MAB) 17-1A IN COMBINATION WITH GM-CSF IN THE TREATMENT OF COLORECTAL-CARCINOMA (CRC)

Unconjugated monoclonal antibodies (MAb) and granulocyte macrophage-co lony stimulating factor (GM-CSF) may induce tumor regression in patien ts. Antibody-dependent cellular cytotoxicity (ADCC) is considered to b e one of the effector functions of MAb. Human peripheral blood mononuc lear cells (PBMC) preincubated with GM-CSF and used as effector cells in an 18h ADCC assay with SW948 (human colorectal carcinoma cell line) as target cells and MAb 17-lA induced significant increase in the lyt ic capacity of the effector cells. Based on these findings the therape utic effect of the combination of mouse MAb 17-lA (IgG2a) against colo rectal carcinoma (CRC) cells and GM-CSF was evaluated in 20 patients- with metastatic CRC. The patients received GM-CSF (250 mug/m2/day s.c. ) for 10 days and a single i.v. infusion of MAb 17-IA (400 mg) at day 3 of the cycle. The cycles were repented with an interval of one month . Four cycles were given. ADCC as well as Fc-receptor bearing mononucl ear cells increased significantly during therapy. Two patients achieve d CR (10%). One patient had an MR (5%) and a further three patients we re considered to have SD > 3 months (15%). The two CR patients are sti ll in CR, 35+ and 30+ months respectively after initiation of therapy. Patients with an ADCC activity at start of therapy above the median v alue of the total patient material survived significantly longer than those patients with an ADCC reactivity below this value (p = 0.002).