Discussion and Conclusion
The present results suggest that CTL are inducible in almost all cases of cultured renal carcinoma cells displaying MHC class-I expression. The CTL showed autologous target-specific cytotoxicity, although the specificity was weak in two cases, Pt.46-CTL against Hpt.10 carcinoma cells and TUHR4TKB-CTL against TUHR3TKB carcinoma cells (Table II). The cytotoxicity was inhibited by previous treatment of the CTL with anti-CD3 antibody (data not shown). No evident cytotoxicity against normal renal epithelial cells was observed in the 6 cases examined so far, suggesting that the antigens might not be expressed on normal cells. This situation is different from the case of melanoma patients in which the CTL generated from TIL effective against autologous melanoma cells also lysed normal melanocytes.1, 5) It is considered possible that the TIL had been primed to differentiate into CTL because of continuous contact with tumor cells in vivo. Therefore, CTL should be generated from TIL in the case of all melanoma patients. However, although tumor-specific CTL could be isolated from 9 of 24 cases through the culture of TIL with repeated stimulation by autologous melanoma cells,29) effective lymphocytes could not be generated in 62.5% of the 24 cases.
The generation of highly active CTL and the 90% success in induction of CTL against MHC class-I expressing renal carcinoma cells may possibly be ascribed to use of the cocktail of IL-1, -2, -4 and -6, while most researchers have used only IL-2 throughout the entire culture process. IL-6 and IL-1 accelerate the development of cytotoxicity,30, 31) and IL-4 mediates the functional differentiation of CD8+ T cells.31) The combined cocktail must have cooperatively promoted the process of induction of CTL. In the case of patient Hpt.16, the generation of CD4+ CTL was evident (Table I). The killing activity of these cells was as strong and as specific for autologous carcinoma as that of the CD8+ CTL from patient Hpt.15. At present, we have no evidence to explain why CD4+ CTL were preferentially generated in this patient. Since the cross reactivity of CTL of Hpt.10, Hpt.15, Pt.46 TUHR3TKB, and TUHR10TKB against allogeneic targets expressing common HLA-A2402 was generally low (Table II), unique antigens might have been expressed on the renal carcinoma cells from each case.
The present results suggest that there are many immature lymphocytes in peripheral circulation that might be educated to attack autologous renal carcinoma cells. To provide sufficient amount of CTL, the present induction technique of CTL can be combined to the expansion techinique of T lymphocytes using anti-CD3 antibody stimulation21) to overcome possible shortage of the autologous target cells for restimulation in the CTL culture. If there are any allogeneic tumor cells expressing common renal carcinoma antigens on their cell surface, they may also be useful. These may contribute to adoptive immunotherapy of renal cancer patients in which expression of MHC class-I molecules is detected on the carcinoma cells.
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|Liu, SQ; (1998). High rate of induction of human autologous cytotoxic T lymphocytes against renal caricinoma cells cultured with an interleukin cocktail. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/|
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