LAK細胞の発現する膜結合型リンフォトキシンの癌細胞障害活性の解析

点击翻译按钮获取中文摘要

This research was aimed to improve clinical effects of adoptive immunotherapy of cancer. For this purpose, mechanisms underlying the target tumor cell killing of LAK cells were investigated from the point of membrance-associated lymphotoxin (mLT) expressred on LAK cells, which we originally reported. In an attempt trying to investigate using cloned cells, cloning of LAK cells were carried out. Several lines of LAK cell clones were established, however, the expression of mLT on all these clones were too low to use them in the analysis of mLT.Therefore, conventional LAK cells were employed in this research. Using conventional LAK cells, several novel evidences came out. Novel tumor cell killing activity of LAK cells other than conventional NK and LAK killing activity were indentified, which was closely related with mLT but not soluble secreted LT.The novel killing activity was evident in a short term killing assay system using ^<51>Cr but not necessarily evident on long term killing assay which was related with cytokine secreted by LAK cells. The effect of mLT was executed via unidentified receptor but via two TNF receptors, to which soluble LT binds and sends signals. LAK cells expressing mLT up-regulated ICAM-1 expression on target tumor cells, which plays important role in target tumor cell killing by LAK cells. This up-regulating effect on ICAM-1 expression by LAK cells was not exerted by mLT itself, but by an unidenntified membrane factor on LAK cells. This effect was not exerted by soluble factors secreted by LAK cells. The identification of the mLT-related ICAM-1 up-regulating membrane factor of LAK cells would bring out an improvement in adoptive immunotherapy.