The construction and in vitro testing of photo-activatable cancer targeting folated anti-CD3 conjugates.
The construction and in vitro testing of a photo-activatable anti-tumour immuno-regulatory antibody is described. In this 'cloaked' folated anti-CD3 antibody conjugate, the folate portion of the conjugate is free to bind to folate receptor expressing cancer cells, whilst the anti-CD3 activity is effectively rendered inert by a coating of photo-labile 2-nitrobenzyl groups. On irradiation with UV-A light the activity of the anti-CD3 antibody is restored, not only when it is required, but more importantly, only where it is required. The conjugate can then attract killer T-cells to the surface of the tumour cells and kill them. Unirradiated normal tissues, to which the conjugate has been targeted by specific and non-specific binding, remain unharmed. We believe that these 'photo-switchable' conjugates could be used to markedly improve the targeting of the immune response to folate receptor (FR) expressing ovarian and breast cancers whilst minimising the side effects in the rest of the body.
Thompson
Stephen
S
Diagnostic and Therapeutic Technologies, School of Clinical and Laboratory Sciences, University of Newcastle Upon Tyne, The Medical School, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK.
Dessi
John
J
Self
Colin H
CH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000528:radiation effects; D017252:CD3 Complex / Q000276:immunology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D005260:Female; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex