Enhancement of lymphokine-activated killer cell induction using anti-CD25 and anti-CTLA-4 monoclonal antibodies.
Immunosuppression may contribute to cancer progression, in which regulatory T (T-reg) cells have been demonstrated to play important roles. We investigated whether anti-CD25 (alpha-CD25) monoclonal antibody (mAb) and anti-cytotoxic T lymphocyte-associated antigen-4 (alpha-CTLA-4) mAb could augment in vitro proliferation and cytotoxic activity against cancer cell lines of lymphokine-activated killer (LAK) cells. Human LAK cells with immobilized alpha-CD3 Ab plus IL-2 were significantly augmented, including LAK/alpha-CD25 (10 microg ml, p=0.045) and LAK/alpha-CTLA-4 (5 microg/ml, p=0.025; 10 microg/ml, p=0.019). LAK/alpha-CD25 and LAK/alpha-CTLA-4 showed significant cytotoxic activities against gastric cancer cell lines (p<0.05). The phenotype of LAK cells showed that alpha-CD25 and alpha-CTLA-4 mAb more selectively induced the phenotype of CD8+ cells. The secretion of IFN-gamma increased significantly in LAK/alpha-CTLA-4 (p=0.032). alpha-CD25 mAb reduced intracellular CTLA-4 (p=0.0069), and alpha-CTLA-4 mAb reduced intracellular FOXP3 (p=0.049), respectively. These results suggest that LAK cells are highly augmented in the presence of alpha-CD25 mAb and alpha-CTLA-4 mAb through the possible mechanism of the suppression of T-reg.
Okita
Riki
R
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan.
Yamaguchi
Yoshiyuki
Y
Emi
Akiko
A
Matsuura
Kazuo
K
Toge
Tetsuya
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000187:drug effects*; D000943:Antigens, Differentiation / Q000187:drug effects*; D060908:CTLA-4 Antigen; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation; D009369:Neoplasms / Q000276:immunology*; D010641:Phenotype
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D007371:Interferon-gamma