Open AccessEnhancement of T Cell Receptor Signaling of Tumor‐infiltrating Lymphocytes by Retrovirally Mediated fyn Gene Transduction
Author(s) -
Fujita Kazuyuki,
Ikarashi Hirokazu,
Takakuwa Koichi,
Kodama Shoji,
Akagi Tsuyoshi,
Yamamoto Tadashi,
Tanaka Kenichi
Publication year - 1994
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1994.tb02909.x
Subject(s) - fyn , transduction (biophysics) , signal transduction , cancer research , gene , biology , receptor , microbiology and biotechnology , immunology , genetics , biochemistry , tyrosine kinase
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‐β ( P <0.05) than nontransduced TILs. These results could have important implications for TILs‐mediated gene therapy for cancer.