Abstract
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 mm3, 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.
| Original language | English |
|---|---|
| Pages (from-to) | 600-607 |
| Number of pages | 8 |
| Journal | Journal of Immunology |
| Volume | 171 |
| Issue number | 2 |
| Publication status | Published - Jul 15 2003 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
Cite this
Antitumor and antimetastatic activity of IL-23. / Lo, Chia Hui; Lee, Shan Chih; Wu, Pin Yi; Pan, Wen Yu; Su, Jui; Cheng, Chao Wen; Roffler, Steve R.; Chiang, Bor Luen; Lee, Chun Nan; Wu, Cheng Wen; Tao, Mi Hua.
In: Journal of Immunology, Vol. 171, No. 2, 15.07.2003, p. 600-607.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antitumor and antimetastatic activity of IL-23
AU - Lo, Chia Hui
AU - Lee, Shan Chih
AU - Wu, Pin Yi
AU - Pan, Wen Yu
AU - Su, Jui
AU - Cheng, Chao Wen
AU - Roffler, Steve R.
AU - Chiang, Bor Luen
AU - Lee, Chun Nan
AU - Wu, Cheng Wen
AU - Tao, Mi Hua
PY - 2003/7/15
Y1 - 2003/7/15
N2 - 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 mm3, 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.
AB - 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 mm3, 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.
UR - http://www.scopus.com/inward/record.url?scp=0037769934&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037769934&partnerID=8YFLogxK
M3 - Article
C2 - 12847224
AN - SCOPUS:0037769934
VL - 171
SP - 600
EP - 607
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -