Comparative activity of Sant7 and anti-IL-6, IL-6R monoclonal antibodies in a murine model of B-cell lymphoma.
Interleukin-6 (IL-6) plays a central role in the pathogenesis of several autoimmune and inflammatory diseases as well as B-cell lymphoproliferative disorders. This work describes the effects of the recombinant or adenovirally-delivered IL-6 superantagonist Sant7, anti-IL-6 and IL-6 receptor monoclonal antibodies in a severe murine model of human B-cell lymphoma induced in SCID mice by transplantation of an LCL-41 cell line variant (isotype-switched IgM>IgG). Survival of 60% of the animals treated with anti-gp130 was observed up to day 33, while about 20% of the animals survived with anti-gp80 and Sant7 treatment. No survival was observed with the anti-IL-6 monoclonal antibody treatment. No significant change in serum and peritoneal levels of human IL-6 (hIL-6) and soluble human IL-6 receptor (shIL-6R) was observed in the recombinant Sant7-treated group towards the control group. The anti-gp80 monoclonal antibody induced significant increase of both hIL-6R and hIL-6 in serum and peritoneum. The anti-gp130 monoclonal antibody treatment determined a reduction of the seric shIL-6R and a significant increase of the seric hIL-6. Anti-IL-6 monoclonal antibody administration resulted in a reduction of serum and in an increase of peritoneal hIL-6. Treatment with adenoviral Sant7 was associated with a reduction of circulating shIL-6R, hIgG and mSAP. However, only marginal anti-tumor efficacy of the adenoviral Sant7 was observed. Overall, the present data suggest a potential for anti-hIL-6 therapy in B-cell lymphomas. Less severe animal models might be useful to better evaluate Sant7 efficacy alone or in combination with other anti-IL-6 therapeutics.
Campo
Silvia
S
Department of Immunology, Sigma-Tau SpA R&D, Via Pontina Km 30400, Pomezia 00040, Rome, Italy. silvia.campo@sigma-tau.it
Serlupi-Crescenzi
Ottaviano
O
Arseni
Brunilde
B
Rossi
Stefania
S
Saggio
Isabella
I
Salone
B
B
Cherubini
G
G
Carminati
Paolo
P
De Santis
Rita
R
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D015703:Antigens, CD / Q000096:biosynthesis; D002460:Cell Line; D045744:Cell Line, Tumor; D050822:Cytokine Receptor gp130; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D007249:Inflammation; D015850:Interleukin-6 / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000276:immunology*; D011994:Recombinant Proteins / Q000737:chemistry; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018076:DNA, Complementary; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D007074:Immunoglobulin G; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; C432252:SANT-7; D050822:Cytokine Receptor gp130