Abstract

Introduction

Materials & Methods

Results

Discussion & Conclusion

References

Discussion
Board

CTL have been suggested as effective killer cells in adoptive immunotherapy for tumors.1-3) Due to the prerequisite need for tumor cells or tumor-derived antigens to be present as continuous stimulation for induction and proliferation of CTL, recent studies have focused mainly on identification of tumor antigens1-3) and preliminary therapy for tumors.4, 5) This is presumably because a system for reproducible generation of human autologous CTL has not been established yet, as neither established autologous tumor cell lines nor tumor-derived antigenic peptides for repeated stimulation of the lymphocytes are available. To replace autologous tumor cells, autologous tumor-specific CTL generated using HLA-matched tumor cells6, 7) or peptide pulsed antigen-presenting cells8-10) have been developed. Although there have been many reports of mutations frequently occurring in some specific genes, including genes encoding tumor-related proteins such as p53,11) the MAGE family,12) and HER-2/neu,13) tumor cells show a diversity of mutations in their DNA which may give rise to a variety of antigens.14-17) To overcome this problem, gene manipulation or hybridization of the tumor cells and antigen-presenting cells have been employed to enhance the antigenicity or to strengthen the interaction between tumor cells and lymphocytes.17-19) However, these manipulations always require a considerably large number of tumor cells and these are impossible to obtain in many cases of human tumors.20)

For clinical application of CTL, it is necessary to confirm that human autologous CTL are inducible in almost all the cases. Recently, we established an induction technique involving stimulation with tumor cells and/or fixed tumor sections for alloreactive21, 22) and autologous23) CTL by applying a cocktail consisting of 4 ILs.24) Here, we report that highly reproducible induction of autologous CTL was achieved in renal carcinoma patients, in a study aimed to establish a routine protocol for induction of CTL for renal cancer immunotherapy.

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