Human recombinant TNF-alpha on localization of 90Y-radioantibody in human tumour xenografts.

Abstract

The effect of recombinant human tumour necrotic factor-alpha (TNF-alpha) on the intratumour and whole-body distributions of 90Y-labelled C110 anticarcinoembryonic antigen (CEA) monoclonal antibody (MAb) was studied using nude mice bearing two different tumours. The nude mice were injected subcutaneously with the CEA-positive LS174T colorectal cancer xenograft and the CEA-negative H-MESO-1 malignant mesothelioma xenograft. One hour before injection of radiolabelled MAb, mice were injected intravenously with human recombinant TNF-alpha (3 mg per mouse) or saline, and biodistributions of radiolabel were determined by tissue counting and whole-body autoradiography (ARG). Twenty-four hours after injection, TNF-alpha administration increased radioactivity in the LS174T tumour by 57% (17.30 +/- 1.61 vs. 9.83 +/- 1.55% ID g-1, P < 0.01), while decreasing radioactivity in blood and other normal organs. Diminished but similar effects on radioantibody biodistribution were seen at 48 and 72 hours. TNF-alpha did not affect specific MAb localization in the control H-MESO xenograft. Tumour:blood ratios were increased from 0.7 to 1.7 at 24 h with TNF-alpha administration. Pretreatment with TNF-alpha may be of value in increasing specific localization of monoclonal antibodies in tumour tissue.