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Clinical Cancer Research Vol. 9, 4653-4665, October 15, 2003
© 2003 American Association for Cancer Research

Perspectives

Targeted Anti-Interleukin-6 Monoclonal Antibody Therapy for Cancer

A Review of the Rationale and Clinical Evidence

Mohit Trikha1, Robert Corringham, Bernard Klein and Jean-François Rossi

Centocor, Malvern, Pennsylvania 19355 [M. T., R. C.], and Unit of Cellular Therapy and INSERM U475 [B. K.] and Service d’Hématologie et d’Oncologie Médicale and INSERM U475 [J-F. R.], Montpellier, France 34295

ABSTRACT

Interleukin (IL)-6, a pleiotropic cytokine with varied systemic functions, plays a major role in inflammatory processes. It modulates the transcription of several liver-specific genes during acute inflammatory states, particularly C-reactive protein, and controls the survival of normal plasmablastic cells. In addition, IL-6 has been implicated in hematopoiesis as a cofactor in stem cell amplification and differentiation. This article is the first review of clinical studies in the 1990s with anti-IL-6 monoclonal antibodies (mAbs) in the treatment of patients with cancer and related lymphoproliferative disorders. In six clinical studies of mAbs to IL-6 with BE-8 or CNTO 328 in patients with multiple myeloma, renal cell carcinoma, and B-lymphoproliferative disorders, anti-IL-6 mAb treatment decreased C-reactive protein levels in all patients. In most patients, levels decreased below detectable limits. The antibodies were well tolerated, and no serious adverse effects were observed in the vast majority of studies. The fact that anti-IL-6 mAb therapy decreased the incidence of cancer-related anorexia and cachexia may also be useful in the treatment of cancer patients.




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