Autor: |
Iwashiro, Michihiro, Jinyan, Wang, Toda, Masaaki, Linan, Wang, Kato, Takuma, Kuribayashi, Kagemasa |
Zdroj: |
International Immunology; Dec2002, Vol. 14 Issue 12, p1459-1468, 10p |
Abstrakt: |
To attain one of the final goals for cancer immunotherapy, cytotoxic T lymphocyte (CTL) clones were selected on the basis of exogenous IL‐2 independence after limiting dilution culture from mixed lymphocyte tumor cell culture cells of FBL‐3 tumor‐immune spleens. About 10% of the clones could be propagated up to >5 times by weekly passages in the presence of splenic feeder and stimulating tumor cells. Two of the representative FBL‐3‐specific CTL clones that were able to undergo the fifth passage were expanded in large numbers for adoptive transfer by two rounds of a weekly passage with medium containing IL‐2. FBL‐3‐specific CTL clones thus obtained showed a strong ability to eliminate the established tumors when transferred into tumor‐bearing nude mice. In addition, the cells were recovered from the mouse spleen even 8 months after the transfer. The most striking differences between the CTL clones used in this experiment and those maintained conventionally in the presence of IL‐2 were the abilities to produce IL‐2 by themselves and the high expression level of the integrin molecule, VLA‐4, that disappeared when cultured completely in the continuous presence of IL‐2 in vitro during 12 weeks. In addition, concomitant with the disappearance of exogenous IL‐2 independence and VLA‐4 expression, the CTL clones lost their capacity to eradicate the tumor in vivo. Thus, the higher capacity of CTL clones to produce IL‐2 on their own seemed to be correlated with the in vivo efficacy for tumor eradication and the long‐term maintenance of their physiological profiles typical of memory T cells. [ABSTRACT FROM PUBLISHER] |
Databáze: |
Complementary Index |
Externí odkaz: |
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