m17-1A-, c17-1A- and cSF25-mediated antibody-dependent cell-mediated cytotoxicity in patients with advanced cancer.
The anti-tumour antibody-dependent cell-mediated cytotoxicity (ADCC) capacity of the conventional antibody m17-1A was compared with its chimerised analogue c17-1A and a newer chimeric antibody, cSF25, specific for colonic adenocarcinoma. The results (AUC units +/- s.e.m., control versus cancer) show that mononuclear cells from patients with adenocarcinoma mediate ADCC as efficiently as those from controls for m17-1A (143 +/- 14 vs 153 +/- 14), c17-1A (174 +/- 16 vs 189 +/- 14) cSF25 (215 +/- 18 vs 237 +/- 13) and effectors and targets alone (57 +/- 9 vs 51 +/- 8). Both chimeric antibodies mediated ADCC more effectively than m17-1A with cSF25 consistently producing the highest lysis. Furthermore, more efficient ADCC was found to correspond with monocyte activation examined flow cytometrically. The results (mean channel fluorescence) show that HLA-DR expression is increased with c17-1A (1436 +/- 200) and cSF25 (2252 +/- 298) above that observed when effectors and targets were incubated alone (1157 +/- 168) or with m17-1A (1286 +/- 170). Similarly, interleukin 2 receptor (IL-2R) expression (percentage of positive cells) was augmented in the presence of m17-1A (15 +/- 3), c17-1A (14 +/- 3) and cSF25 (25 +/- 3) when compared with no antibody (9 +/- 2). We discuss the possibility that the superior ADCC activity of chimeric antibodies, especially cSF25, may be due to increased monocyte activation.
Pullyblank
A M
AM
Academic Surgical Unit, Imperial College of Science, Technology and Medicine, St Mary's Hospital, London, UK.
Guillou
P J
PJ
Monson
J R
JR
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D000918:Antibody Specificity; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy; D005260:Female; D006801:Humans; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins