Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy

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 autologo...

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Main Authors: Lina Guo, Jinsong Ding, Wenhu Zhou
Format: Article
Language:English
Published: Elsevier 2023-12-01
Series:Acta Pharmaceutica Sinica B
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211383523003349
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author Lina Guo
Jinsong Ding
Wenhu Zhou
author_facet Lina Guo
Jinsong Ding
Wenhu Zhou
author_sort Lina Guo
collection DOAJ
description 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.
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spelling doaj.art-f9b7f851b96242578da4d6da2dc517852023-11-25T04:47:46ZengElsevierActa Pharmaceutica Sinica B2211-38352023-12-01131250745090Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapyLina Guo0Jinsong Ding1Wenhu Zhou2Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, ChinaXiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China; Key Laboratory of Biological Nanotechnology of National Health Commission, Xiangya Hospital, Changsha 410008, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2211383523003349Bacteria-mediated cancer therapyTumor microenvironmentCalcium carbonateMineralizationMetalloimmunologyAutologous tumor vaccine
spellingShingle Lina Guo
Jinsong Ding
Wenhu Zhou
Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy
Acta Pharmaceutica Sinica B
Bacteria-mediated cancer therapy
Tumor microenvironment
Calcium carbonate
Mineralization
Metalloimmunology
Autologous tumor vaccine
title Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy
title_full Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy
title_fullStr Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy
title_full_unstemmed Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy
title_short Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy
title_sort converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy
topic Bacteria-mediated cancer therapy
Tumor microenvironment
Calcium carbonate
Mineralization
Metalloimmunology
Autologous tumor vaccine
url http://www.sciencedirect.com/science/article/pii/S2211383523003349
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