Cytokine-binding proteins: stimulating antagonists

Klein, Bernard; Brailly, Hervέ

doi:10.1016/0167-5699(95)80161-8

Cited by 95 publications

(61 citation statements)

References 40 publications

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“…We have previously shown that the B-E8 anti-IL-6 mAb was no longer able to block gp130 IL-6 transducer activation induced by IL-6 when the mAb/IL-6 ratio was less than 250. 29 …”

Section: Calculation Of Daily Il-6 Productionmentioning

confidence: 99%

“…We found that prolonged anti-IL-6 treatment in association with DEX and HDM was feasible, did not affect haematopoietic recovery but reduced HDM-related toxicities. In addition, using the original methodology developed by our group, 24,29,30 we demonstrated for the first time a dramatic increase in IL-6 production after HDM. These data confirm the potential importance to block IL-6 that is a main myeloma cell survival factor, to avoid the rescue of some myeloma cells after HDM.…”

Section: Logous Transplantationmentioning

confidence: 99%

“…29 Out of the 24 patients treated with anti-IL-6-DEX-HDM140, 13 (54%) were in CR (four patients) or in VGPR (nine patients). Six patients were in PR and five had a minimal response.…”

Section: Clinical Responsementioning

confidence: 99%

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Optimizing the use of anti-interleukin-6 monoclonal antibody with dexamethasone and 140 mg/m2 of melphalan in multiple myeloma: results of a pilot study including biological aspects

Rossi

Fégueux

et al. 2005

Bone Marrow Transplant

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Summary:Interleukin-6 (IL-6) is a major survival factor for multiple myeloma (MM) cells preventing apoptosis induced by dexamethasone (DEX) or chemotherapy. In all, 24 consecutive patients with MM in first-line therapy received DEX for 4 days, followed by melphalan (HDM: 140 mg/m 2 ) and autologous stem cell transplantation (ASCT). The anti-IL-6 monoclonal antibody (mAb) (B-E8) was given till haematological recovery, starting 1 day before DEX. Results were historically compared to MM patients treated with HDM 140 and 200 mg/m 2 . Our results show (1) that B-E8 was able to fully neutralize IL-6 activity in vivo before and after HDM as shown by inhibition of C reactive protein (CRP) production; (2) no haematological toxicity; (3) a significant reduction of mucositis and fever; (4) a median event-free survival of 35 months and an overall survival of 68.2% at 5 years with a median follow-up of 72 months; and (5) the overall daily IL-6 production progressively increased on and after 7 days post-HDM, with the increased serum CRP levels. In the 5/24 patients with uncontrolled CRP production, a large IL-6 production was detected (320 lg/day) that could not possibly be neutralized by B-E8. These data show the feasibility to neutralize IL-6 in vivo with anti-IL-6 mAb in the context of HDM. Bone Marrow Transplantation (2005) 36, 771-779.

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“…We have previously shown that the B-E8 anti-IL-6 mAb was no longer able to block gp130 IL-6 transducer activation induced by IL-6 when the mAb/IL-6 ratio was less than 250. 29 …”

Section: Calculation Of Daily Il-6 Productionmentioning

confidence: 99%

Section: Logous Transplantationmentioning

confidence: 99%

See 1 more Smart Citation

Optimizing the use of anti-interleukin-6 monoclonal antibody with dexamethasone and 140 mg/m2 of melphalan in multiple myeloma: results of a pilot study including biological aspects

Rossi

Fégueux

et al. 2005

Bone Marrow Transplant

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“…The relative concentrations of sIL-~R, sgpl30 and IL-6 in serum may thus, in part, determine their physiological effects. For a review of the pharmacokinetic characteristics in vivo of human cytokine-binding proteins see Klein & Brailly (1995).…”

Section: Soluble Il-6r and Gp130: Physiological Roles?mentioning

confidence: 99%

Interleukin‐6: Structure‐function relationships

et al. 1997

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Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-1 1, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affhity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.

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“…A effect'. 10,11 The use of receptor antagonists rather than wide range of cells are susceptible to Ad infection, high mAbs, is an innovative and promising approach for the virus titers are readily obtainable and extremely treatment of cytokine-mediated disease states. These molefficacious gene transfer has been described in several ecules act by specifically binding cytokine receptors in animal models.…”

Section: Introductionmentioning

confidence: 99%