Antitumor and antimetastatic activity of IL-23.
The structure and T cell stimulatory effects of the recently discovered cytokine IL-23 are similar to, but distinct from, those of IL-12. Although the antitumor activities of IL-12 are well characterized, the effect of IL-23 on tumor growth is not known. In this study, murine CT26 colon adenocarcinoma and B16F1 melanoma cells were engineered using retroviral vectors to release single-chain IL-23 (scIL-23) to evaluate its antitumor activity. In BALB/c mice, scIL-23-transduced CT26 cells grew progressively until day 26 to an average size of 521 +/- 333 mm(3), then the tumors started to regress in most animals, resulting in a final 70% rate of complete tumor rejection. scIL-23 transduction also significantly suppressed lung metastases of CT26 and B16F1 tumor cells. In addition, mice that rejected scIL-23-transduced tumors developed a memory response against subsequent wild-type tumor challenge. Compared with scIL-12-expressing CT26 cells, scIL-23-transduced tumors lacked the early response, but achieved comparable antitumor and antimetastatic activity. These results demonstrated that IL-23, like IL-12, provided effective protection against malignant diseases, but it probably acted by different antitumor mechanisms. As a first step in identifying these antitumor mechanisms, tumor challenge studies were performed in immunocompromised hosts and in animals selectively depleted of various lymphocyte populations. The results showed that CD8(+) T cells, but not CD4(+) T cells or NK cells, were crucial for the antitumor activity of IL-23.
Lo
Chia-Hui
CH
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Lee
Shan-Chih
SC
Wu
Pin-Yi
PY
Pan
Wen-Yu
WY
Su
Jui
J
Cheng
Chao-Wen
CW
Roffler
Steve R
SR
Chiang
Bor-Luen
BL
Lee
Chun-Nan
CN
Wu
Cheng-Wen
CW
Tao
Mi-Hua
MH
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000517:prevention & control* / Q000556:secondary*; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000517:prevention & control*; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000627:therapeutic use; D007156:Immunologic Memory / Q000235:genetics; D007279:Injections, Subcutaneous; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D008546:Melanoma, Experimental / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C508841:Il23a protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins