Selectivity of Antibody-Targeted Anthracycline Antibiotics on T Lymphocytes

Abstract
Targeted polymeric prodrugs based on N-(2-hydroxypropyl) methacrylamide were tested on human peripheral blood lymphocytes or mouse splenocytes triggered in vitro to proliferation by T cell specific (Con A) or B cell specific (S. aureus Cowan 1) mitogens. Only a selective inhibition of 3H- thymidine incorporation by T lymphocytes was observed after in vitro incuba tion with prodrugs prepared by covalent attachment of daunomycin or adriamycin and antibody (anti-CD3; anti Thy 1.2) to biodegradable oligopeptide side chains of soluble synthetic copolymer HPMA. The in vitro results were confirmed in vivo by inhibition of antibody response to thymus dependent (ARS-BGG) or thymus independent (TNP-E. coli) antigens in normal Balb/c mice and in athymic nu/nu Balb/c mice. After administration of biocompatible, antibody targeted prodrugs only the antibody response against ARS-BGG was considerably reduced.

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