The therapeutic use of the unconjugated monoclonal antibodies (MAb) 17-1A in combination with GM-CSF in the treatment of colorectal carcinoma (CRC)

Abstract

Unconjugated monoclonal antibodies (MAb) and granulocyte macrophage-colony stimulating factor (GM-CSF) may induce tumor regression in patients. Antibody-dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of MAb. Human peripheral blood mononuclear 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 17-1A induced significant increase in the lytic capacity of the effector cells. Based on these findings the therapeutic effect of the combination of mouse MAb 17-1A (IgG2a) against colorectal carcinoma (CRC) cells and GM-CSF was evaluated in 20 patients with metastatic CRC. The patients received GM-CSF (250 micrograms/m2/day s.c.) for 10 days and a single i.v. infusion of MAb 17-1A (400 mg) at day 3 of the cycle. The cycles were repeated with an interval of one month. Four cycles were given. ADCC as well as Fc-receptor bearing mononuclear cells increased significantly during therapy. Two patients achieved CR (10%). One patient had an MR (5%) and a further three patients were considered to have SD > 3 months (15%). The two CR patients are still in CR, 35+ and 30+ months respectively after initiation of therapy. Patients with an ADCC activity at start of therapy above the median value of the total patient material survived significantly longer than those patients with an ADCC reactivity below this value (p = 0.002).