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A gp130 Interleukin-6 Transducer-Dependent SCID Model of
Human Multiple Myeloma
Cosette Rebouissou,
John Wijdenes,
Patrick Autissier,
Karin Tarte,
Valerie Costes,
Janny Liautard,
Jean-Francois Rossi,
Jean Brochier, and
Bernard Klein
From the Institute for Molecular Genetics, CNRS, Montpellier, France;
the Diaclone, Besançon, France; INSERM U475, Montpellier, France;
and the Service des Maladies du Sang B, CHU Montpellier, Hôpital
Lapeyronie, Montpellier, France.
Agonist antihuman gp130 transducer monoclonal antibodies (MoAbs)
were used in SCID mice to grow myeloma cells whose survival and
proliferation is dependent on gp130 transducer activation. The agonist
anti-gp130 MoAbs neither bound to murine gp130 nor activated murine
cells and, as a consequence, did not induce interleukin-6 (IL-6)-related toxicities in mice. They have a 2-week half-life in
vivo when injected in the peritoneum. The agonist antibodies made
possible the in vivo growth of exogenous IL-6-dependent human myeloma
cells as well as that of freshly explanted myeloma cells from 1 patient
with secondary plasma cell leukemia. Tumors occurred 4 to 10 weeks
after myeloma cell graft and weighed 3 to 5 g. They grew as solid
tumors in the peritoneal cavity and metastasized to the different
peritoneal organs: liver, pancreas, spleen, and intestine. Tumoral
cells were detected in blood and bone marrow of mice grafted with the
XG-2 myeloma cells. Tumoral cells grown in SCID mice had kept the
phenotypic characteristics of the original tumoral cells and their in
vitro growth required the presence of IL-6 or agonist anti-gp130 MoAbs.
Myeloma cells from 4 patients with medullary involvement persisted for
more than 1 year as judged by detectable circulating human Ig. However,
no tumors were detected, suggesting a long-term survival of human
myeloma cells without major proliferation. These observations
paralleled those made in in vitro cultures as well as the tumor growth
pattern in these patients. This gp130 transducer-dependent SCID model
of multiple myeloma should be useful to study various therapeutical
approaches in multiple myeloma in vivo.
Blood, Vol. 91 No. 12 (June 15), 1998:
pp. 4727-4737
© 1998 by The American Society of Hematology.
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