Application of target-specific drug immunoconjugates to experimental bone marrow replacement therapy in mice

• Published in: Cancer research (Chicago, Ill.) Vol. 50; no. 5; pp. 1538 - 1543
• Main Authors: LEI DING, LIZHANG YU, SHUSHENG XIE, DONGER GONG, VERGIDIS, R, DIENER, E
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.03.1990
• Subjects: Animals; Antibodies, Monoclonal - pharmacology; Antineoplastic agents; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow Diseases - drug therapy; Bone Marrow Transplantation; Cell Line; Chemotherapy; Daunorubicin - pharmacology; Female; Graft vs Host Disease - prevention & control; Hematopoiesis - drug effects; Immunotoxins - pharmacology; Isoantibodies - pharmacology; Lymphoma - drug therapy; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred DBA; Pharmacology. Drug treatments; T-Lymphocytes; Transplantation, Homologous; Transplantation, Isogeneic; Antineoplastic agent; Immunochemotherapy; Rodentia; Monoclonal antibody; Lymphoma; Vertebrata; Autograft; Mammalia; Depletion; Mouse; Spacer; Bone marrow; Drug targeting; Graft; Syngeneic system; Tumor cell; Comparative study
• ISSN: 0008-5472; 1538-7445

Immunoconjugates whose cytotoxic component consists of a phytopeptide are often used as purging agents in bone marrow replacement therapy. Less popular are drug immunoconjugates containing a small molecular weight cytotoxic drug attached to the target-specific conjugand via an appropriate spacer molecule. High target specificity, resistance of the drug to intralysosomal proteases and, once cleaved from the spacer, ready exist of the drug from the lysosome are among the advantages drug immunoconjugates hold over phytotoxin immunoconjugates. The cytotoxic drug daunomycin attached via an acid-sensitive spacer to monoclonal antibody of appropriate specificity was shown to purge murine bone marrow of contaminating tumor cells without affecting its hematopoietic potential. Lethally irradiated mice reconstituted with syngeneic bone marrow from which contaminating lymphoma cells had been removed survived indefinitely. Furthermore, lymphoma-bearing mice, provided they were sufficiently irradiated to eliminate tumor cells in situ, were successfully reconstituted with fully allogeneic bone marrow from which potentially graft-versus-host-reactive T-cells had been purged.