Preparation and biological characterization of conjugates consisting of ricin and a tumor-specific non-internalizing MAb.

Abstract:

:MOv18, a non-internalizing monoclonal antibody (MAb) with restricted tumor specificity, was conjugated to ricin toxin (RT). According to their ability to bind to galactose residues of Sepharose 6B, the immunoconjugates were fractionated into Bound and Unbound MOv18-RT. The two conjugates could be distinguished by SDS-PAGE, in vivo toxicity and agglutination capability. When the binding activity of both fractions was compared by solid-phase RIA to that of native MAb, it proved to be similar on the relevant target cells but significantly increased on the non relevant cells. On the latter, galactose totally cancelled the binding of the Unbound immunoconjugate, whereas it could only partially reverse that of the Bound MOv18-RT. By in vitro cytotoxic activity, either in the presence or absence of galactose, only a slight selectivity for relevant versus non-relevant target cells was observed for both conjugates. It seems that in the presence of a MAb which is incapable of internalization, the conjugate cytotoxicity could only be attributed to RT, with a loss of the MAb's specificity.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Cogliati T,Brusa P,Canevari S,Caldera M,Mezzanzanica D,Dosio F,Cattel L,Colnaghi MI

subject

Has Abstract

pub_date

1991-01-01 00:00:00

pages

417-21

issue

1

eissn

0250-7005

issn

1791-7530

journal_volume

11

pub_type

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