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Immunotoxin-mediated Inhibition of Chronic Lymphocytic Leukemia Cell Proliferation in Humans¹

Cristina Gandini Bone Marrow Transplantation Unit, Division of Medical Oncology, Istituto Nazionale Tumori, Via Venezian 1, Milan 20133 [S. S., M. B., A. F., G. B., A. M. G.]; Renal Transplantation Unit, Division of Nephrology [B. B.] and Division of Hematology [P. M.], Ospedale Niguarda-Cà Granda, Milan 20162; and Immunology Line, Farmitalia Carlo Erba, Milan 20146 [D. A. L.], Italy

We evaluated the cytotoxicity of the immunotoxin OKT1-SAP on fresh B-chronic lymphocytic leukemia (B-CLL) cells from 31 consecutive patients. OKT1-SAP comprised the OKT1 (CD5) monoclonal antibody disulfide linked to saporin-6 (SAP) ribosome-inactivating protein from the plant Saponaria officinalis. The effect of OKT1-SAP on target CD5-positive CD5-positive B-CLL cells was estimated using an in vitro proliferation inhibition assay in which control or OKT1-SAP-treated B-CLL cells were induced to proliferate by sequential stimulation with insolubilized anti-C3b receptor CB04 (CD35) antibody and low molecular weight B-cell growth factor. In 90% of patients, OKT1-SAP specifically suppressed B-CLL cell proliferation in a dose-related manner (50% inhibitory concentration, 4.0–6.8 nM). Taken together the findings reported in this article provide information relevant to the clinical development of immunotoxins because: (a) the in vitro conditions under which B-CLL cell proliferation is inhibited by OKT1-SAP are achievable in vivo without nonspecific toxicity according to our previous toxicology and pharmacokinetic studies in primates; and (b) the B-CLL cell proliferation inhibition assay described here provides a basis for future comparative studies.

¹ This study was partially supported by CNR Grant 87-01519-44 to A. M. G.

² To whom requests for reprints should be addressed.

Received 11/15/88. Revised 3/ 6/89. Accepted 3/22/89.