Oral administration of a soluble 1-3, 1-6 beta-glucan during prophylactic survivin peptide vaccination diminishes growth of a B cell lymphoma in mice.
beta-glucans are biological response modifiers with activatory effects on macrophages, dendritic cells (DC), granulocytes and NK cells. In this study, we investigated the effect of a soluble yeast-derived beta-(1-3), (1-6)-D-glucan on prophylactic peptide vaccination against the B cell lymphoma A20 in syngeneic Balb/c mice. We found that repeated immunizations with two MHC class-I restricted peptides derived from the tumor antigen survivin combined with oral co-administration of beta-glucan could significantly diminish intradermal tumor growth, whereas peptide vaccination alone failed to control tumor growth. beta-glucan as single agent induced only a weak but non-significant growth inhibitory effect. To determine whether the tumor inhibitory effect of the combined treatment was associated with the induction of a tumor-specific immune response we quantified splenic DC and macrophages, analyzed the maturation of DC and measured the frequency of peptide-specific CD8+ and CD4+ T cells. Treated mice showed significantly increased numbers of splenic macrophages and mature DC compared to untreated tumor-bearing mice. After restimulation with both peptides in vitro elevated levels of interferon (IFN)-gamma-secreting CD8+ T cells were found in two of four tested mice following treatment and one of four mice showed a strong increase of interleukin (IL)-4-secreting CD4+ T cells. Our data reveal a beneficial effect of beta-(1-3), (1-6)-D-glucan in tumor growth inhibition by tumor-specific peptide vaccination which may rely on a function of the polymeric sugar as immunological adjuvant.
Harnack
Ulf
U
Medical Clinic of Oncology and Hematology, Charité-Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany.
Eckert
Klaus
K
Fichtner
Iduna
I
Pecher
Gabriele
G
D000284:Administration, Oral; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D005936:Glucans / Q000008:administration & dosage / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects; D051034:Inhibitor of Apoptosis Proteins; D016393:Lymphoma, B-Cell / Q000628:therapy*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008869:Microtubule-Associated Proteins / Q000008:administration & dosage / Q000276:immunology*; D012097:Repressor Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000077022:Survivin; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage
C117749:Birc5 protein, mouse; D005936:Glucans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D012097:Repressor Proteins; D000077022:Survivin; D022223:Vaccines, Subunit; C033671:epiglucan