Antibody-dependent cell-mediated cytotoxicity in human cancer: characterization of patient leukocyte activity and treatment effects.

Abstract

Antibody-dependent cell-mediated cytotoxicity (ADCC), medicated by peripheral blood Hypaque-Ficoll separated mononuclear cells, was studied in humans using chicken erythrocytes (CRBC) incubated in a 1:1200 dilution of rabbit anti-CRBC and human B erythrocytes (HRBC) incubation in a 1:20 dilution of isoantibody. At the optimal target effector ratio of 3:1, ADCC to both CRBC and HRBC was significantly higher than normal in 27 lung cancer, 18 malignant melanoma, and seven colon cancer patients, but not in 20 breast cancer patients. Chemotherapy (single-agent or combination) in 12 patients did not effect ADCC in vitro but significantly suppressed ADCC to both targets after only four or five days of therapy in vivo (ADCC to CRBC, 47.4 to 24.1% lysis: ADCC to HRBC, 48.1 to 16.3% lysis). Immunotherapy with intravenous (IV) corynebacterium parvum or IV methanol extraction residue of BCG (MER) boosted ADCC to both targets within four to seven days of the first dose. It was found that ADCC to HRBC but not to CRBC was completely absent in three cases of active hairy cell leukemia but was present in two cases in remission. The ADCC to HRBC showed an age-dependent increase in both the 51 normal subject and the cancer patients. This was not observed for ADCC to CRBC. The ADCC to CRBC was mediated mainly by an Fc-receptor-positive, nonadherent, small lymphocyte, and ADCC to HRBC was mediated entirely by an adherent monocyte. The ADCC did not correlate significantly with the H3 thymidine incorporation of peripheral blood mononuclear cells, cultured without stimulation for either one or seven days. It also did not correlate with the number of residual granulocytes in the mononuclear cell suspensions. Measurement of ADCC is a useful method of characterizing host defense in malignant disease and its modification by therapy.