Cytokine Therapy for Cancer

M.      Tagawa

doi:10.2174/1381612003400597

Abstract

Modulation of immune responses by the use of recombinant cytokines or cytokine genes is one of the strategies for cancer therapy. Although host immune responses are complex and many kinds of cells are involved, crucial steps for enhancing anti-tumor responses can be induced by a single or a few cytokines administered. However, cytokines may induce toxic reactions or produce no substantial effects, when the concentration is inappropriate. Administration of recombinant cytokine(s) has advantages in controlling the blood concentration and the biological activity that can be induced by the cytokine. Since cytokines are relatively unstable in vivo, cancer patients have to receive a large amount of the recombinant protein to maintain the required blood concentration for biological activity. Administration of the protein is thereby often toxic to the patients. In contrast, secretion of the cytokine from tumor or vehicle cells by gene transfer is another therapeutic maneuver. Previous preclinical studies have shown that cytokines which facilitate type 1 helper T (Th1) cells-mediated immune reactions but not Th2 cells-mediated reactions, when produced in tumors, are effective for anti-tumor responses. Several technical problems to express sufficient amounts of cytokines in appropriate target cells remain unresolved but the potential of cytokine gene therapy is being explored. Cytokine therapy trials also contributes to our present knowledge of how anti-tumor responses can be efectively produced in cancer patients, shedding the light on the generation of tumor-specific immunity in the patients.

Keywords: Cytokine therapy, cancer, recombinant, genes, antitumor response, immune, TH1, cytotoxic T lymphocytes, NK Cell, MART 1, Th2 effectir function, TNFA, IFN y production, vaccine, fas ligand, Natural killer, Major histocompatibility complex, Antigen presenting cell, Dendritic, CD40 ligand, Tumor necrosis factor, interleukin, Interferon, Granulocyte macrophage colony stimulating, Type 1 helper T, Lymphokine activated, Inducible protein 10, Monokine induced, Severe combined immunodeficient, Prostate specific antigen