Combination tumor immunotherapy with radiotherapy and Th1 cell therapy against murine lung carcinoma.
Mice bearing established Lewis lung carcinoma (LLC) expressing model tumor antigen, ovalbumin (OVA) (LLC-OVA) marginally responded to local radiotherapy, but none of the mice was cured. In contrast, treatment of the tumor-bearing mice with intratumoral injection of tumor-specific T helper type 1 (Th1) cells and tumor antigen (OVA) after radiotherapy dramatically prolonged the survival days and induced complete cure of the mice at high frequency (80%). Radiation therapy combined with Th1 cells or OVA alone showed no significant therapeutic activity against LLC-OVA. Such a strong therapeutic activity was not induced by intratumoral injection of Th1 cells plus OVA. Compared with other treatment, radiation therapy combined with Th1 cells and OVA was superior to induce the generation of OVA/H-2(b) tetramer(+) tumor-specific cytotoxic T lymphocyte (CTL) with a strong cytotoxicity against LLC-OVA in draining lymph node (DLN). Moreover, the combined therapy is demonstrated to inhibit the growth of tumor mass, which grew at contralateral side. These results indicated that radiotherapy combined with Th1 cell/vaccine therapy induced a systemic antitumor immunity. These findings suggested that combination therapy with radiotherapy and Th1 cell/vaccine therapy may become a practical strategy for cancer treatment.
Yokouchi
Hiroshi
H
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, N-15, W-7, Kita-ku, Sapporo 060-0815, Japan.
Chamoto
Kenji
K
Wakita
Daiko
D
Yamazaki
Koichi
K
Shirato
Hiroki
H
Takeshima
Tsuguhide
T
Dosaka-Akita
Hirotoshi
H
Nishimura
Masaharu
M
Yue
Zhang
Z
Kitamura
Hidemitsu
H
Nishimura
Takashi
T
D000818:Animals; D000951:Antigens, Neoplasm / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D003131:Combined Modality Therapy; D016219:Immunotherapy, Adoptive; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000637:transplantation*
D000951:Antigens, Neoplasm; D010047:Ovalbumin