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IL-21 Enhances Tumor-Specific CTL Induction by Anti-DR5 Antibody Therapy
Author(s) -
Mark J. Smyth,
Yoshihiro Hayakawa,
Erika Cretney,
Nadeen Zerafa,
Pallavur V. Sivakumar,
Hideo Yagita∥,
Kazuyoshi Takeda
Publication year - 2006
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.176.10.6347
Subject(s) - ctl* , immunotherapy , cancer research , apoptosis , medicine , tumor cells , t cell , cytokine , immunology , biology , antigen , immune system , cd8 , biochemistry
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.

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