FAILURE TO INCREASE THE IN VIVO IMMUNOSUPPRESSIVE ACTIVITY OF ANTILYMPHOCYTE GLOBULIN BY CONJUGATION WITH MELPHALAN

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Abstract
An attempt was made to increase the in vivo immunosuppressive powers of antilymphocyte globulin (ALG) by conjugating it with melphalan (MEL), an alkylating agent, via an inert intermediate carrier (polyglutamic acid). Careful controls to distinguish between increased activity attributable to the conjugate per se, as opposed to synergy between the components of the complex, were included. Conjugation did not destroy the alkylating properties of the drug nor the cytotoxic activity of the antibody. The effect of MEL-ALG complexes on skin allograft survival in inbred and outbred [mouse] strains were appraised. In neither system did the immunosuppressive powers of the conjugate exceed those of ALG alone, regardless of the dose used. Alkylating drugs are not suitable for this particular purpose.