Combinations of tumor-specific CD8+ CTLs and anti-CD25 mAb provide improved immunotherapy.
One new approach to cancer therapy is based on the adoptive transfer of tumor-specific cytotoxic T cells and anti-CD25 antibodies. In the present study, CD8+ and IFN-gamma secreting T lymphocytes (CTLs) were enriched as tumor-specific cytotoxic T cells from spleen lymphocytes of mice bearing the Renca tumor (a murine renal carcinoma line originating from a BALB/c mouse) after stimulation with tumor cells. An anti-CD25 IL-2Ralpha(anti-CD25) mAb from hybridoma PC61 was used for depletion for CD4(+)CD25(+) regulatory T (Treg) cells. Treatment-efficacy for tumor-bearing mice was compared using 4 systems: 1, whole spleen lymphocytes stimulated with tumor cells in vitro from tumor-bearing mice; 2, CTLs; 3, anti-CD25 mAbs; 4, CTLs and anti-CD25 mAbs. At the 50th day after tumor inoculation, in the group which received anti-CD25 mAb for depletion of T cells and inoculation of CTLs, tumors had disappeared and no re-growth was observed. In contrast, all mice of the non-treated and other three groups, treated with whole spleen cells alone, CTLs alone and anti-CD25 mAb alone, had died. These results showed that a combination of Treg cell-depletion using anti-CD25 mAbs and CTL administration is a feasible approach for treatment of cancers which warrants further exploration in the clinical setting.
Ohmura
Yukinobu
Y
Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan.
Yoshikawa
Kazuhiro
K
Saga
Shinsuke
S
Ueda
Ryuzo
R
Kazaoka
Yoshiaki
Y
Yamada
Shiro
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002859:Chromium Isotopes / Q000737:chemistry; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis*; D008495:Medical Oncology / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
D000911:Antibodies, Monoclonal; D002859:Chromium Isotopes; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma