Combination of adoptive cell transfer and antibody injection can eradicate established tumors in mice--an in vivo study using anti-OX40mAb, anti-CD25mAb and anti-CTLA4mAb-.
Boosting an effective immune response against established tumors remains a difficult challenge. This study shows the combination of 1) adoptive cell transfer using CD25 depleted splenocytes co-cultured with irradiated tumor cells, and 2) antibody injection therapy using CTLA4 blockade, the elimination of Treg and OX40, which together could eradicate an established MethA tumor in over 50% of the BALB/c mice. Each element of the protocol was shown to be necessary, as elimination of any factor except anti-CD25 antibody injection failed to eradicate the tumor.
Watanabe
Akira
A
Department of Cardiovascular, Thoracic and General Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. awaw@fc.miyazaki-u.ac.jp
Hara
Masaki
M
Chosa
Eiichi
E
Nakamura
Kunihide
K
Sekiya
Ryo
R
Shimizu
Tetsuya
T
Onitsuka
Toshio
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D003131:Combined Modality Therapy; D016219:Immunotherapy, Adoptive / Q000379:methods*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000276:immunology; D053262:Receptors, OX40 / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse