RESUMO
Myeloid-derived suppressor cells(MDSC) play critical roles in immune escape of tumor. We hypothesized that elimination of tumor-induced MDSCs might help to block tumor growth. Therefore, we constructed a cholera toxin B based peptide vaccine that targets a MDSC surface marker S100A8. Immunized BALB/c mice with CTB-S100A8 plus aluminum hydroxide induced high titers of anti-S100A8 antibodies and reduced tumor burden significantly in 4T1 mice model. We also found the vaccination led to significant reduction of tumor-induced monocytic MDSC(M-MDSC), with no effect on innate MDSCs, dendritic cell(DC) and macrophage(Mφ), demonstrating that targeting tumor-induced MDSC may be a promising approach in cancer immunotherapy.
Assuntos
Calgranulina A/antagonistas & inibidores , Vacinas Anticâncer , Células Mieloides/efeitos dos fármacos , Neoplasias/terapia , Vacinas de Subunidades Antigênicas , Animais , Linhagem Celular Tumoral , Macrófagos , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Induction of cytotoxic T lymphocytes (CTL) is critical to cancer vaccine based immunotherapy. Efforts to elicit CTLs against tumor MUC1 with peptide based vaccine have not been successful in clinical application. We have design a MUC1 vaccine by replacing B cell epitope of CTB with MUC1 VNTR peptide. Immunization with hybrid CTB-MUC1 plus aluminum hydroxide and CpG adujuvant (CTB-MUC1-Alum-CpG) induce MUC1-specific CTLs in mice. Moreover, this vaccination can prevent tumor growth and reduce tumor burden in MUC1+B16 mice model. Meanwhile, CTB-MUC1-Alum-CpG vaccination can promote Th1 cells and CD8+ T cells inflate to tumor tissue. Our approach might be applicable to other cancer vaccine design.