Enhancement of T cell receptor signaling of tumor-infiltrating lymphocytes by retrovirally mediated fyn gene transduction.
We conducted retrovirally mediated transduction of fyn gene into tumor-infiltrating lymphocytes (TILs) in an attempt to augment T cell receptor-CD3 complex signal transduction, using TILs obtained from six patients with epithelial ovarian cancer. The expression of the transduced gene was more than five times that of endogenous fyn gene. In all preparations, the cytolytic activity of the TILs against autologous tumor cells, but not allogeneic tumor cells, was significantly enhanced (P < 0.01) by transduction of fyn gene. In addition, when TILs were treated with anti-CD3 antibody to stimulate T cell receptor-CD3 complex, fyn-gene-transduced TILs showed about two times higher proliferation (P < 0.05) and secreted 2.2 to 11.7 times more tumor necrosis factor-beta (P < 0.05) than nontransduced TILs. These results could have important implications for TILs-mediated gene therapy for cancer.
Fujita
K
K
Department of Obstetrics and Gynecology, Niigata University School of Medicine.
Ikarashi
H
H
Takakuwa
K
K
Kodama
S
S
Akagi
T
T
Yamamoto
T
T
Tanaka
K
K
D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051076:Proto-Oncogene Proteins c-fyn; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics*; D015398:Signal Transduction
D011518:Proto-Oncogene Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn