Immunological effects of BCG as an adjuvant in autologous tumor vaccines.
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.
Li
Q
Q
Division of Surgical Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA.
Normolle
D P
DP
Sayre
D M
DM
Zeng
X
X
Sun
R
R
Jiang
G
G
Redman
B D
BD
Chang
A E
AE
D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000906:Antibodies / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D010641:Phenotype; D014407:Tumor Cells, Cultured; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000906:Antibodies; D001500:BCG Vaccine; D018106:CD28 Antigens; D017252:CD3 Complex; D019496:Cancer Vaccines; D007376:Interleukin-2