Immune enhancement and anti-tumour activity of IL-23.

Immunotherapy, including the use of cytokines and/or modified tumour cells immune stimulatory cytokines, can enhance the host anti-tumour immune responses. Interleukin-23 (IL-23) is a relative novel cytokine, which consists of a heterodimer of the IL-12p40 subunit and a novel p19 subunit. IL-23 has biological activities similar to but distinct from IL-12. IL-23 can enhance the proliferation of memory T cells and the production of IFN-gamma, IL-12 and TNF-alpha from activated T cells. IL-23 activates macrophages to produce TNF-alpha and nitric oxide. IL-23 can also act directly on dendritic cells and possesses potent anti-tumour and anti-metastatic activity in murine models of cancer. IL-23 can also induce a lower level of IFN-gamma production compared with that induced by IL-12. This may make IL-23 an alternative and safer therapeutic agent for cancer, as IL-12 administration can lead to severe toxic side effects because of the extremely high levels of IFN-gamma it induces.

Antitumor activity and immune enhancement of murine interleukin-23 expressed in murine colon carcinoma cells.

Interleukin (IL)-23, a cytokine composed of p19 and the p40 subunit of IL-12, can enhance the proliferation of memory T cells and production of IFN-gamma from activated T cells. It can also induce antitumor effects in murine model. To further evaluate the antitumor activity and immune enhancement of IL-23 in vivo, murine colon carcinoma cells retrovirally transduced with mIL-23 gene were injected subcutaneously (s.c.) into BALB/c mice. Survival time and tumor volume were observed. LDH release assay, [3H]-TdR incorporation assay and ELISA were used to determine CTL activity, proliferation of splenocytes and level of cytokines, respectively. Number of dendritic cells (DCs) was analyzed by flow cytometry (FCM). IL-23 secreted by Colon26/IL-23 cells suppressed the growth of tumor and prolonged the survival time of mice, enhanced proliferation of splenocytes, CTL activity, and number of DCs. IL-23 also promoted the production of Th1 cytokines such as IFN-gamma, IL-12 and TNF-alpha. However, the level of IL-4 was not enhanced significantly. These data suggested that IL-23 secreted by tumor cells can induce antitumor activity by enhancing immune response.

[Expression of IL-23 gene in murine colon carcinoma cells transduced with recombinant retrovirus and its anti-tumor activity].

AIM: To obtain murine colon carcinoma cell lines stably transducted by recombinant retrovirus encoding mIL-23 gene. METHODS: The retrovirus vector was used to transduce the mIL-23 gene into murine colon carcinoma cells (Colon26) and stable clones expressing mIL-23 (Colon26/IL-23) were obtained by screening with G418. The expression of mIL-23 gene was detected by PCR and RT-PCR. The amount of mIL-23 secreted from Colon26/IL-23 cells and IFN-gamma production by murine splenocytes induced by mIL-23 were determined by ELISA. MTT colorimetry was used to assess the in vitro growth of Colon26/IL-23 cells. BALB/c mice were injected s.c. with Colon26/IL-23 cells to observe their tumorigenicity. RESULTS: Colon26/IL-23 cells were set up. Colon26/IL-23 could secrete mIL-23 which could induce the IFN-gamma production by murine splenocytes. The growth of Colon26/IL-23 cells was similar to that of Colon26 cells in vitro. But the tumorigenicity of Colon26/IL-23 cells was lower than that of Colon26 cells in vivo. CONCLUSION: Colon26/IL-23 cells secreting mIL-23 were obtained and IL-23 had anti-tumor activity.