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Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor therapy. However, its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment (ITM). Here, we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate (CaCO3) biomineralized Salmonella (Sal) as an in-situ cancer vaccine producer and systematical ITM regulator. CaCO3 can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading, and such biomineralization did not affect the bioactivities of the bacteria. Upon intratumoral accumulation, the CaCO3 shell was decomposed at an acidic microenvironment to attenuate tumor acidity, accompanied by the release of Sal and Ca2+/A23187. Specifically, Sal served as a cancer vaccine producer by inducing cancer cells' immunogenic cell death (ICD) and promoting the gap junction formation between tumor cells and dendritic cells (DCs) to promote antigen presentation. Ca2+, on the other hand, was internalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system, including DCs maturation, macrophages polarization, and T cells activation. As a result, such bio-vaccine achieved remarkable efficacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility. This work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.
RESUMO
Objective:The explore the mechanism of active immunotherapy with autologous tumor vaccine and clinical significance.Methods:30 patients with advanced tumors were enrolled in this study.4 weeks after operation,the patients received vaccinations of autologous tumor vaccine every 7～10 days for 4 times as adjuvant active immunotherapy,3 days before and 7 days after administrations:peripheral blood monuclear cells(PBMC) were isolated to assay the alteration of proportions of CD + 8 IFN ? + and CD + 8 IL 10 +,CD + 4 IFN ? + and CD + 4 IL 10 + cells.Meanwhile,serum IFN ? and IL 10 were measured within 48 hours after the skin tests with PPD and autologous tumor antigen,diameters of erythemas or indurations were observed.The clinical follow up was performed.Results:After active immunotherapy with autologous tumor vaccine.①The serum IFN ? was increased from (5.98?2 40)pg/ml to (11.20?4.76) pg/ml(P
RESUMO
PURPOSE: Antitumor effect of granulocyte macrophage colony-stimulating factor (GM-CSF)- producing murine colon cancer cells was elucidated against intrahepatic challenge of parental cancer cells, which is clinically relevant tumor model. MATERIALS AND METHODS: Using a model of liver metastasis by intrahepatic challenge of CT-26 murine colon carcinoma cells to syngeneic BALB/c mice, GM-CSF producing cells were given as a intradermal vaccine either 14 days prior to hepatic challenge, or in animals with established tumors. Tumor volume and survival were determined. RESULTS: Animals receiving vaccination showed significant systemic protection against the hepatic challenge of parental tumor cells, and in animals with established hepatic tumors significant response was observed with some prolongation in survival. CONCLUSION: It is concluded that GM-CSF-producing autologous tumor vaccine was effective for the protection of host agaisnt the metastatic hepatic tumor model. Even though its efficacy against the established tumor was not as significant as in protection, GM-CSF producing autologous tumor vaccine can provide support for the specific immunotherapy for the metastatic liver cancer.