Growth and immortalization of human myeloma cells in immunodeficient severe combined immunodeficiency mice: a preclinical model.
Human multiple myeloma (MM) purified tumour cells readily undergo apoptosis in vitro. Interleukin 6 (IL-6), a main growth factor of tumour cells, has enabled the development of IL-6-dependent MM cell lines. Recently, we developed anti-gp130 monoclonal antibodies (mAbs), two of which (B1 + I2) were able to dimerize gp130 and replace IL-6 in vitro. We show here that the injection of B1 + I2 IL-6 agonistic mAbs via the inguinal subcutaneous (SC) route efficiently produced tumours in severe combined immunodeficiency (SCID) mice grafted with IL-6-dependent myeloma cell lines compared with either the intraperitoneal (IP) or abdominal surgical bursa (SB) routes. The SC tumour graft, together with Matrigel and vascular endothelial growth factor (VEGF), leads to a strong vascularization and early detection of serum human immunoglobulins (huIgs). SCID mice treated with B1 + I2 mAbs were injected with fresh MM cells from five patients, four of whom had consistent levels of huIgs, and tumour growth was present in two. For one patient, tumour plasma cells that were passed several times subcutaneously in new SCID mice, still expressed their initial markers after several months. They remained unable to grow in vitro in the presence of B1 + I2 or IL-6. The nature of the SCID factors involved and the triggered genes are under investigation.
Rème
T
T
INSERM U475, Montpellier, France. reme@montp.inserm.fr
Gueydon
E
E
Jacquet
C
C
Klein
B
B
Brochier
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002455:Cell Division; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000494:pharmacology; D005260:Female; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000819:agonists* / Q000494:pharmacology; D007797:Laminin / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D016513:Mice, SCID; D023421:Models, Animal; D009025:Morpholines / Q000276:immunology*; D009101:Multiple Myeloma; D011509:Proteoglycans / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000637:transplantation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D015850:Interleukin-6; D007797:Laminin; D008222:Lymphokines; D009025:Morpholines; D011509:Proteoglycans; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C059485:matrigel; C005759:2-phenyl-5,5-dimethyltetrahydro-1,4-oxazine; D003094:Collagen