Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy.
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.
Takeda
Kazuyoshi
K
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bukyou-ku, Tokyo 113-8421, Japan. ktakeda@med.juntendo.ac.jp
Yamaguchi
Noriko
N
Akiba
Hisaya
H
Kojima
Yuko
Y
Hayakawa
Yoshihiro
Y
Tanner
Jane E
JE
Sayers
Thomas J
TJ
Seki
Naoko
N
Okumura
Ko
K
Yagita
Hideo
H
Smyth
Mark J
MJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001219:Aspartate Aminotransferases / Q000097:blood; D007111:Immunity, Cellular / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D015674:Mammary Neoplasms, Animal / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011961:Receptors, Fc / Q000276:immunology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D011961:Receptors, Fc; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505640:Tnfrsf10b protein, mouse; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase