Immunological effects of BCG as an adjuvant in autologous tumor vaccines

The role of Bacillus Colmette-Guerin (BCG) as an adjuvant in autologous tum or vaccines was examined. In nine patients with renal cell cancer, irradiat ed tumor cells alone (wild-type, WT) or with BCG were inoculated intraderma lly into contralateral thighs. Seven to 10 days later, the draining vaccine -primed lymph modes (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 activat ed in vitro with anti-caa 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 irr adiated autologous tumor targets and cytokines (IFN-gamma, GM-CSF, IL-10) r eleased into the supernatants were measured 24 h later. Anti-CD3/CD28-activ ated BCG-VPLN cells were found to have a greater release of IFN-gamma compa red with that of WT-VPLN cells, which was not observed significantly with I L-10 or GM-CSF. BCG; resulted in increased VPLN cell yield as well as enhan ced type 1 (IFN-gamma release) immune responses of VPLN cells to autologous tumor without upregulating type 2 (IL-IO release) responses. Anti-CD3/CD28 was superior to anti-CDS activation in this cellular response. (C) 2000 Ac ademic Press.