Improving tumor-to-normal-tissue ratios of antibodies by extracorporeal immunoadsorption based on the avidin-biotin concept: development of a new treatment strategy applied to monoclonal antibodies murine L6 and chimeric BR96.
BACKGROUND
Several strategies have been explored to accelerate monoclonal antibody (MAb) conjugate clearance without affecting intratumoral uptake. One of the most promising is extracorporeal immunoadsorption (ECIA), in which excess radiolabeled MAb circulating in blood is removed.


METHODS
Extracorporeal immunoadsorption (ECIA) based on the avidin-biotin concept enables direct adsorption of radiolabeled and biotinylated MAb from plasma and consequently increases the tumor-to-normal-tissue uptake ratio by reducing background radioactivity in all radiosensitive organs. Because the concept is based on an antibody's being biotinylated prior to injection, the blood clearance efficiency is independent of the idiotype or isotype of the antibody employed. As a result, there is no need to develop new adsorption columns for each antibody system used. We have technically simplified the method recently by removing biotinylated MAb directly from blood without separation from plasma preceding the removal. The current study focused on both the development of ECIA and evaluating the effects of ECIA in terms of tumor targeting with two biotinylated radiolabeled MAbs that have different biokinetics, namely, murine MAb L6 and chimeric Mab BR96.


RESULTS
The start time of ECIA should be determined for each MAb individually before radioimmunotherapy and be based on previous tumor biokinetics. BR96 with rapid tumor targeting seems more suitable than L6 for the ECIA procedure; it allows the procedure to start earlier and thereby further reduce whole body activity and exposure of critical organs to radiation.


CONCLUSIONS
ECIA enables direct adsorption of radiolabeled and biotinylated monoclonal antibody from blood and consequently increases the tumor-to-normal-tissue uptake ratio. The method is even applicable to both the internalizing and already highly tumor-selective BR96 in a syngeneic tumor model.
Tennvall
J
J
Department of Oncology, Lund University, Sweden.
Garkavij
M
M
Chen
J
J
Sjögren
H O
HO
Strand
S E
SE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001360:Avidin; D019921:Biotinylation; D007163:Immunosorbent Techniques; D051379:Mice; D016499:Radioimmunotherapy; D051381:Rats
D000911:Antibodies, Monoclonal; D001360:Avidin