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Cytokines Play an Essential Role in Intercellular Communication

Cytokines Play an Essential Role in Intercellular Communication. Asadullah K, et al. Clin Exp Dermatol . 2002;27:578-584. Tumor Necrosis Factor. • 1890s: William Coley Coley ’ s Toxin: Bacterial preparation of Streptococcus pyogenes - First published cancer immunotherapy paper

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Cytokines Play an Essential Role in Intercellular Communication

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  1. Cytokines Play an Essential Role in Intercellular Communication Asadullah K, et al. Clin Exp Dermatol. 2002;27:578-584.

  2. Tumor Necrosis Factor • 1890s: William Coley Coley’s Toxin: Bacterial preparation of Streptococcus pyogenes - First published cancer immunotherapy paper Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas: with a report of ten original cases. Am. J. Med Sci. 1893; 105: 487-511. - Treated ~ 900 patients presenting with inoperable cancers. - 10% cure rate

  3. Interleukin-2 • T cell growth factor • Induces the activation and proliferation of cytotoxic T-lymphocytes • Enhances the cytolytic ability of NK cells • Mediates antitumor activity in vivo

  4. December, 1985

  5. Interleukin-2 Toxicity • Commonly: Fever, chills, lethargy, diarrhea, nausea, anemia, confusion. • Induces a capillary leak syndrome with major fluid shifts. • Hypotension, Azotemia • ICU monitoring, vasopressors • Neutrophil chemotactic defect predisposing patients to gram positive bacteria. • Mortality of 1% (down from 5%).

  6. Interleukin-2 and MelanomaRenal Cell Carcinoma • High Dose IL-2 • 600,000 to 720,000 IU/kg IV q8o on days 1-5 and 15 -19. • Repeat at 8 to 12 week intervals in responding patients • Tumor Response: 15-20% • Complete Response: 4-6% and durable. IL-2 approved for metastatic melanoma in 1993 and for RCC later.

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