IL-21 enhances tumor-specific CTL induction by anti-DR5 antibody therapy.
Tumor cell apoptosis is the basis of many cancer therapies, and tumor-specific T cells are the principal effectors of successful anti-tumor immunotherapies. In this study, we show that induction of tumor cell apoptosis by agonistic mAb against DR5, combined with delayed IL-21 treatment, suppressed tumor growth and pre-established tumor metastases. Synergistic effects of the combination were observed in several tumor models where the target tumor was sensitive to DR5-mediated apoptosis. IL-21 promoted tumor-specific CTL activity and enhanced memory responses to tumor rechallenge. These results indicate that a rational combination of Ab-based therapy that causes tumor cell apoptosis and a cytokine that promotes T cell memory is a useful new strategy for cancer immunotherapy.
Smyth
Mark J
MJ
Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Center, A'Beckett Street, Victoria 8006, Australia. mark.smyth@petermac.org
Hayakawa
Yoshihiro
Y
Cretney
Erika
E
Zerafa
Nadeen
N
Sivakumar
Pallavur
P
Yagita
Hideo
H
Takeda
Kazuyoshi
K