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Antitumor activity of anti-CD30 immunotoxin (Ber-H2/saporin) in vitro and
in severe combined immunodeficiency disease mice xenografted with human
CD30+ anaplastic large-cell lymphoma
L Pasqualucci, M Wasik, BA Teicher, L Flenghi, A Bolognesi, F Stirpe, L Polito, B Falini and ME Kadin
Institute of Hematology, University of Perugia, Italy.
To develop a novel adjunctive therapy for CD30 (Ki-1)+ anaplastic large-
cell lymphoma (ALCL), we investigated in preclinical studies the antitumor
activity of an immunotoxin (IT) constructed by coupling the plant
ribosome-inactivating protein saporin (SO6) to the monoclonal antibody
(MoAb) Ber-H2 that is directed against the CD30 molecule, a new member of
the tumor necrosis factor receptor (TNFR) super-family. The activity of
Ber-H2/SO6 IT was tested both in vitro against the CD30+ ALCL-derived cell
line JB6 and in vivo using our severe combined immunodeficiency disease
(SCID) mouse model of human xenografted CD30+ ALCL. In vitro, the
Ber-H2/SO6 IT was selectively and highly toxic to the JB6 cell line [50%
inhibiting concentration (IC50), 3.23 x 10(-12) mol/L as SO6]. In vivo, a
3-day treatment with nontoxic doses of Ber- H2/SO6 (50% of LD50) induced
lasting complete remissions (CR) in 80% of mice when started 24 hours after
tumor transplantation. In contrast, injection of the IT at later stages of
tumor growth (mice bearing subcutaneous tumors of 40- to 60-mm3 volume),
induced CR in only 6 of 21 (approximately 30%) mice and significantly
delayed tumor growth rate (P < .01). This finding suggests that maximum
effect of the anti-CD30 IT is observed when tumor cell burden is small.
Persistent tumors from IT-treated mice consisted of CD30+ cells, thus
excluding the possibility that selection of CD30-negative mutant clones
during IT therapy was responsible for resistance to treatment. We conclude
that Ber-H2/SO6 IT is an effective agent against CD30+ ALCL growing in SCID
mice, suggesting its possible role as adjuvant therapy in patients with
CD30+ ALCL refractory to standard treatments.
Volume 85,
Issue 8,
pp. 2139-2146,
04/15/1995
Copyright © 1995 by The American Society of Hematology
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