Cytokine Therapy for Cancer

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 effectively produced in cancer patients, shedding the light on the generation of tumor-specific immunity in the patients.

Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of liver cancer

“…An increased level of IL-2 is involved in efficient cellular immune function (31). Previous studies have shown that a locally-secreted high level of IL-2 generates fewer side effects compared with a systemically administered high dose of IL-2 (31,32). In the present study, the low level of IL-2 present during the formation of liver lesions was significantly increased during treatment with LUT.…”

Expression of the interleukin-21 gene in murine colon carcinoma cells generates systemic immunity in the inoculated hosts

“…The mice that had rejected IL-21-producing clones became resistant to Colon 26 cells that were subsequently inoculated, but about a half of them developed irrelevant RL male-1 tumors (Table 1). When the mice were treated with anti-asialo GM 1 ), a half of the mice rejected the mixed tumor cells after forming small tumor masses (Table 1). All the mice that received 5 Â 10 5 parent cells as a control developed tumors progressively.…”

“…1 Cytokines released from T-helper type-1 cells but not type-2 cells have more effectively produced antitumor activities in a number of experimental animal models because the cytokines enhance cell-mediated immunity.…”

Immunotherapy of metastatic melanoma by intratumoral injections of Vero cells producing human IL-2: Phase II randomized study comparing two dose levels

“…38 Although the exact role of types 1 and 2 responses in human tumor immunology remains to be defined, a CTL type of immune response seems to be associated with Th1 cytokines, whereas Th2 cytokines are more often associated with antibody production. 39 It is tempting to speculate that intratumoral treatment with Vero -IL -2 caused a local shift toward a humoral -type rather than a cellular-type immune response, thereby decreasing the effective overall antitumor immunity, and thus explaining the disappointing clinical activity of TG2001.…”