The role of Bacillus Colmette-Guérin (BCG) as an adjuvant in autologous tumor vaccines was examined. In nine patients with renal cell cancer, irradiated tumor cells alone (wild-type, WT) or with BCG were inoculated intradermally into contralateral thighs. Seven to 10 days later, the draining vaccine-primed lymph nodes (WT-VPLN and BCG-VPLN) were excised. BCG increased the number of harvested VPLN cells by 10-fold (mean +/- SE = 61.8 +/- 20.6/x10(-7)/patient). BCG-VPLN had significantly greater percentages of CD3(+) and CD4(+) T cells compared to WT-VPLN. Both groups of VPLN cells were activated in vitro with anti-CD3 or anti-CD3/CD28 mAbs followed by expansion in IL-2. Anti-CD3/CD28 activation resulted in greater expansion of CD4(+) T cells compared to anti-CD3. After activation, VPLN cells were stimulated with irradiated autologous tumor targets and cytokines (IFN-gamma, GM-CSF, IL-10) released into the supernatants were measured 24 h later. Anti-CD3/CD28-activated BCG-VPLN cells were found to have a greater release of IFN-gamma compared with that of WT-VPLN cells, which was not observed significantly with IL-10 or GM-CSF. BCG resulted in increased VPLN cell yield as well as enhanced type 1 (IFN-gamma release) immune responses of VPLN cells to autologous tumor without upregulating type 2 (IL-10 release) responses. Anti-CD3/CD28 was superior to anti-CD3 activation in this cellular response.
Copyright 2000 Academic Press.