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KMID : 0391319910010010064
Korean Journal of Biological Response Modifiers
1991 Volume.1 No. 1 p.64 ~ p.73
Antitumor-Cytotoxic Properties of Human Tumor-Infiltrating Lymphocytes(TIL) Activated With Interleukin 2
Choeh Kyu-Chul

Choi Yong-Mook
Abstract
Many actual interactions between tumors in cancers and the immune system have been demonstrated. Tumor-infiltrating lymphocytes (TIL) are often seen in tumors. Their functional role in the pathogenesis of cancer is unknown. The author studied TIL in 20 patients with 12 stomach cancers, 4 breast cancers, 1 lung cancer, 1 colon cancer, 1 ovarian cancer and 1 cervix cancer.
The amount of TIL obtained was 7.1X105¡¾6.7(SD) cells/cm3 of tumor mass with range of 0.8-27.5 X 105. TIL were expanded between 0.5 and 118,000 fold increases for 10 to 34 days(2-9 subcultures). Partially purified natural IL-2-induced expansions of TIL were more rapid than highly purified recombinant IL-2-induced expansions, and showed 10 times high for 18 days of culture. The majority of TIL were T lymphocytes with range of 56-68.8% of Leu4+, 25.0-40.8% of Leu2a+ and 0-51.5% of Leu3a+cells. With continued in vitro expansion for 14-20 days, there was a concomitant increase in T lymphocytes (Leu4 + ) to 71-76.8%, but the changes of phenotypes of Leu2a+ and Leu3a+ were variable.
TIL were tested for cytotoxicity against fresh autologous and allogenic tumor cells, and Raji and K562 targets in a 4-hr 51Cr release assay. IL-2-activated TIL showed more potent cytotoxicity against autologous tumor targets than allogenic (p<0.025). The cytotoxic activity of activated TIL in killing autologous tumor targets was higher level than that of LAK cells(0.05And the author reviewed the in vitro and in vivo studies on human TIL and determined the followings : 1) the amount of lymphocytes obtained form tumors of cancers, 2) the ability to proliferate in IL-2-conditioned media, 3) materials that can augment the process of IL-2-activation of TIL, 4) the ability to develop cytotoxicity against autologous tumor cells, 5) the immunologic phenotypes, 6) the in vivo distribution, survival and functional longevity of activated TIL, and 7) the results of clinical trials.
The application of TIL in human is still experimental, although the greater efficacy of TIL in combating cancer was shown. Further studies about fine-tuning processes are necessary to establish treatment protocols with high therapeutic efficacy and tolerable side effects.
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