M17-1A-, C17-1A- and CSF25-mediated Antibody-dependent Cell-mediated Cytotoxicity in Patients with Advanced Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 1994 Oct 1

PMID 7917934

Citations 3

Authors

A M Pullyblank

P J Guillou

J R Monson

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Antibody-dependent cytotoxicity mediated by chimeric monoclonal antibody Nd2 and experimental immunotherapy for pancreatic cancer.

Nishihara T, Sawada T, Yamamoto A, Yamashita Y, Ho J, Kim Y Jpn J Cancer Res. 2000; 91(8):817-24.

PMID: 10965023 PMC: 5926427. DOI: 10.1111/j.1349-7006.2000.tb01019.x.

Preoperative clinical radioimmunodetection of pancreatic cancer by 111 In-labeled chimeric monoclonal antibody Nd2.

Sawada T, Nishihara T, Yamamoto A, Teraoka H, Yamashita Y, Okamura T Jpn J Cancer Res. 1999; 90(10):1179-86.

PMID: 10595748 PMC: 5926001. DOI: 10.1111/j.1349-7006.1999.tb00693.x.

Interleukin 1 and tumour necrosis factor alpha may be responsible for the lytic mechanism during anti-tumour antibody-dependent cell-mediated cytotoxicity.

Pullyblank A, Guillou P, Monson J Br J Cancer. 1995; 72(3):601-6.

PMID: 7669568 PMC: 2033875. DOI: 10.1038/bjc.1995.380.

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