EFFECTS OF THE INTERMOLECULAR TOXIN-MONOCLONAL ANTIBODY LINKAGE ON THE INVIVO STABILITY, IMMUNOGENICITY AND ANTILEUKEMIC ACTIVITY OF B43 (ANTI-CD19) POKEWEED ANTIVIRAL PROTEIN IMMUNOTOXIN

We have successfully constructed highly potent and selective anti-CD19 PAP immunotoxins using each of the three crosslinking agents, SPDP, L C-SPDP, or SMPT, to generate an intermolecular bridge between the B43 MoAb and PAP toxin moieties. These immunotoxins were selectively immun oreactive with and cytotoxic against CD19+ B-lineage ALL cells. In thi s report, we compared (a) in vivo chemical, immunological, and biologi cal stability, (b) in vivo immunogenicity, and (c) in vivo anti-leukem ic activity of various B43-PAP immunotoxin constructs. Our data recomm end the use of SPDP and SMPT rather than LC-SPDP for generation of B43 (anti-CD19)-PAP immunotoxins as clinical anti-leukemic agents. To our knowledge, this is the first comparative analysis of the in vivo pharm acokinetic features, immunogenicity, and anti-leukemic activity of ant i-CD19 PAP immunotoxins that were prepared with different heterobifunc tional crosslinking agents.