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Reduction of Immunogenicity by Covalent Modification of Murine and Rabbit Immunoglobulins with Oxidized Dextrans of Low Molecular Weight

Hybritech Incorporated, San Diego, California 92126

This communication describes the covalent modification of monoclonal and polyclonal antibodies with oxidized dextrans of low molecular weight to generate conjugates having low immunogenicity in vivo. Conjugation conditions were optimized to generate monomeric, dextran-modified antibodies, free of both high-molecular-weight polymeric aggregates and unmodified antibodies. Conjugates could be prepared with varying levels of dextran substitution. These conjugates retained optimal immunoreactivity as well as in vivo pharmacokinetics and tumor-localization properties. In addition, multiple i.v. administrations of dextran-modified antibodies in animals did not elicit a measurable immune response to either the antibody or the dextran portion of these conjugates.

¹ To whom requests for reprints should be addressed, at Hybritech, Inc., P. O. Box 269006, San Diego, CA 92126.

Received 4/13/89. Revised 2/22/90.

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