Immunotoxins have been extensively studied for the treatment of
neoplasias; their intracavitary administration could be useful for the
therapy of
tumors confined to the pleural or peritoneum spaces. To study the feasibility of this "locoregional" treatment, a pharmacokinetic study of
immunotoxins delivery is necessary.
Ricin, a plant toxin extracted from the seeds of Ricinus communis, has often been used in
immunoconjugates for its high activity; nevertheless, appropriate strategies have been necessary to limit the aspecific toxicity. We previously prepared a AR-3-ricin
immunotoxin lacking the ability to bind galactosidic cell surface residues, a so-called sterically blocked
immunotoxin. The
monoclonal antibody AR-3, an
IgG1 specific to the
CAR-3 antigen, was able to recognize human colorectal
adenocarcinomas. Preclinical trials in nude mice, intraperitoneally grafted with the target
neoplasia, showed that this
immunotoxin suppressed
tumor growth without showing any undesirable
ricin toxicity. In the present work we report the pharmacokinetic properties of this
immunotoxin, showing the in vivo stability and a relatively long blood survival. With a biodistribution study in
tumor-bearing mice, we demonstrate that in
tumor-invaded tissues, the concentration of the specific AR-3-ricin
immunotoxin was higher and progressively increased in a multiple-dose regimen. In contrast, an irrelevant
immunotoxin behaved differently because it did not show specific
tumor uptake. Moreover the pharmacokinetic data reported in this work improve the potential for "locoregional" treatment of
malignancy with blocked
immunotoxins.