PMID- 16061391 OWN - NLM STAT- MEDLINE DCOM- 20051018 LR - 20051117 IS - 1043-4666 (Print) IS - 1043-4666 (Linking) VI - 31 IP - 5 DP - 2005 Sep 7 TI - Comparative activity of Sant7 and anti-IL-6, IL-6R monoclonal antibodies in a murine model of B-cell lymphoma. PG - 368-74 AB - 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. FAU - Campo, Silvia AU - Campo S AD - Department of Immunology, Sigma-Tau SpA R&D, Via Pontina Km 30400, Pomezia 00040, Rome, Italy. silvia.campo@sigma-tau.it FAU - Serlupi-Crescenzi, Ottaviano AU - Serlupi-Crescenzi O FAU - Arseni, Brunilde AU - Arseni B FAU - Rossi, Stefania AU - Rossi S FAU - Saggio, Isabella AU - Saggio I FAU - Salone, B AU - Salone B FAU - Cherubini, G AU - Cherubini G FAU - Carminati, Paolo AU - Carminati P FAU - De Santis, Rita AU - De Santis R LA - eng PT - Journal Article PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (DNA, Complementary) RN - 0 (IL6ST protein, human) RN - 0 (Il6st protein, mouse) RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-6) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, Interleukin-6) RN - 0 (Recombinant Proteins) RN - 0 (SANT-7) RN - 133483-10-0 (Cytokine Receptor gp130) SB - IM MH - Adenoviridae/genetics MH - Animals MH - Antibodies, Monoclonal/*chemistry MH - Antigens, CD/biosynthesis MH - Cell Line MH - Cell Line, Tumor MH - Cytokine Receptor gp130 MH - DNA, Complementary/metabolism MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Immunoglobulin G/chemistry MH - Inflammation MH - Interleukin-6/*analogs & derivatives/biosynthesis/blood/*immunology/metabolism MH - Lymphoma, B-Cell/immunology/*metabolism MH - Membrane Glycoproteins/biosynthesis MH - Mice MH - Mice, SCID MH - Neoplasm Transplantation MH - Receptors, Interleukin-6/biosynthesis/*immunology MH - Recombinant Proteins/chemistry MH - Time Factors EDAT- 2005/08/03 09:00 MHDA- 2005/10/19 09:00 CRDT- 2005/08/03 09:00 PHST- 2004/12/03 00:00 [received] PHST- 2005/06/01 00:00 [revised] PHST- 2005/06/13 00:00 [accepted] PHST- 2005/08/03 09:00 [pubmed] PHST- 2005/10/19 09:00 [medline] PHST- 2005/08/03 09:00 [entrez] AID - S1043-4666(05)00196-1 [pii] AID - 10.1016/j.cyto.2005.06.006 [doi] PST - ppublish SO - Cytokine. 2005 Sep 7;31(5):368-74. doi: 10.1016/j.cyto.2005.06.006.