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PMID: 14769851 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy.

The Journal of experimental medicine ·Vol. 199 ·No. 4 ·2004-02-16 ·Pages 437-48

Takeda K, Yamaguchi N, Akiba H, Kojima Y, Hayakawa Y, Tanner JE, Sayers TJ, Seki N, Okumura K, Yagita H, Smyth MJ

Abstract

Because tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) preferentially induces apoptosis in tumor cells and plays a critical role in tumor surveillance, its receptor is an attractive target for antibody-mediated tumor therapy. Here we report that a monoclonal antibody (mAb) against the mouse TRAIL receptor, DR5, exhibited potent antitumor effects against TRAIL-sensitive tumor cells in vivo by recruiting Fc receptor-expressing innate immune cells, with no apparent systemic toxicity. Administration of the agonistic anti-DR5 mAb also significantly inhibited experimental and spontaneous tumor metastases. Notably, the anti-DR5 mAb-mediated tumor rejection by innate immune cells efficiently evoked tumor-specific T cell immunity that could also eradicate TRAIL-resistant variants. These results suggested that the antibody-based therapy targeting DR5 is an efficient strategy not only to eliminate TRAIL-sensitive tumor cells, but also to induce tumor-specific T cell memory that affords a long-term protection from tumor recurrence.

MeSH Terms
Alanine Transaminase/blood Animals Apoptosis Regulatory Proteins Aspartate Aminotransferases/blood Immunity, Cellular/immunology Immunotherapy/methods Mammary Neoplasms, Animal/immunology Membrane Glycoproteins/deficiency,genetics,immunology Mice Mice, Inbred BALB C Mice, SCID Receptors, Fc/immunology Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor/immunology T-Lymphocytes/immunology TNF-Related Apoptosis-Inducing Ligand Tumor Necrosis Factor-alpha/deficiency,genetics,immunology
Chemicals
Apoptosis Regulatory Proteins Membrane Glycoproteins Receptors, Fc Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor TNF-Related Apoptosis-Inducing Ligand Tnfrsf10b protein, mouse Tnfsf10 protein, mouse Tumor Necrosis Factor-alpha Aspartate Aminotransferases Alanine Transaminase
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Takeda Kazuyoshi
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bukyou-ku, Tokyo 113-8421, Japan. [email protected]
Yamaguchi Noriko
Akiba Hisaya
Kojima Yuko
Hayakawa Yoshihiro
Tanner Jane E
Sayers Thomas J
Seki Naoko
Okumura Ko
Yagita Hideo
Smyth Mark J
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.20031457
Email
[email protected]
Published
2004-02-16
Epub
2004-00-09
Pages
437-48
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2211825
Subset
IM
Grants
PHS HHS · N01-C0-12400 · United States
External Links
PubMed source DOI: 10.1084/jem.20031457 PMC Full Text View journal details
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