Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens
Background Enhancing antigen cross-presentation is essential for the development of a tumor neoantigen vaccine. One approach is to stimulate antigen-presenting cells (APCs) to uptake neoantigens. Mycobacterium tuberculosis (MTb) contains pathogen-associated molecular patterns (PAMPs) recognized by A...
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BMJ Publishing Group
2025-02-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/2/e010150.full |
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| author | Jie Jiang Feng-Ying Huang Shu-Zhen Dai Guang-Hong Tan Ming-Hui Chen Hengyu Chen Wu-Ping Zheng Ri-Hong Wu Weijing Xie |
| author_facet | Jie Jiang Feng-Ying Huang Shu-Zhen Dai Guang-Hong Tan Ming-Hui Chen Hengyu Chen Wu-Ping Zheng Ri-Hong Wu Weijing Xie |
| author_sort | Jie Jiang |
| collection | DOAJ |
| description | Background Enhancing antigen cross-presentation is essential for the development of a tumor neoantigen vaccine. One approach is to stimulate antigen-presenting cells (APCs) to uptake neoantigens. Mycobacterium tuberculosis (MTb) contains pathogen-associated molecular patterns (PAMPs) recognized by APCs and adhesion molecules that facilitate MTb invasion of APCs. Therefore, we suggest using MTb as a carrier to enhance APC phagocytosis of neoantigens, thereby promoting antigen cross-presentation.Methods The successful preparation of the MTb carrier (phMTb) was confirmed through electron and confocal microscopy. Fluorescence microscopy was used to detect PAMPs and adhesion molecules on phMTb as well as to observe its role in aiding dendritic cells (DCs) in antigen uptake into endosomes or lysosomes. Flow cytometry was used to assess the retention of PAMPs and adhesion molecules on phMTb, investigate antigen uptake by DCs, evaluate their activation and maturation status, examine the presentation of tumor neoantigens, and analyze immune cells in draining lymph nodes and tumor tissues. The efficacy of phMTb vaccine formulations in combination with anti-programmed cell death protein 1 (PD-1) antibody therapy was assessed using the MC38 mouse tumor models. Adverse effects were evaluated through H&E staining of major organs, assessment of reproductive capability and detection of biochemical indices.Results The engineered porous hollow phMTb carrier successfully encapsulated model tumor neoantigens, with or without the adjuvant CpG. The phMTb retained PAMPs and adhesion molecules on its surface, similar to the parental MTb, thereby enhancing DC uptake of phMTb and its formulations containing tumor neoantigens and CpG. Vaccines formulated with phMTb facilitated DC maturation, activation, cross-presentation of tumor neoantigens, and promoted migration of phMTb-laden DCs to lymph nodes, enhancing effector and memory CD8+ T lymphocyte function. In murine tumor models, immunization with phMTb-formulated neoantigen vaccines elicited a robust tumor-specific cytotoxic T lymphocyte immune response with minimal adverse effects. Additionally, vaccination with phMTb-formulated neoantigen vaccines effectively reversed the tumor’s immune-suppressive microenvironment. Concurrent administration of the PD-1 antibody with the phMTb-formulated neoantigen vaccine exhibited significant synergistic therapeutic effects.Conclusions The results of our study highlight the potential clinical translation of personalized tumor neoantigen vaccines using the phMTb carrier. |
| format | Article |
| id | doaj-art-6afe71a7303941fc96a671efd4f30704 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-6afe71a7303941fc96a671efd4f307042025-02-07T07:45:14ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-02-0113210.1136/jitc-2024-010150Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigensJie Jiang0Feng-Ying Huang1Shu-Zhen Dai2Guang-Hong Tan3Ming-Hui Chen4Hengyu Chen5Wu-Ping Zheng6Ri-Hong Wu7Weijing Xie8Public Research Center, Hainan Medical University, Haikou, Hainan, ChinaNHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan, ChinaNHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan, ChinaNHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan, ChinaNHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan, ChinaDepartment of Breast and Thyroid Surgery, The Second Affiliated Hospital, Hainan Medical University, Haikou, Hainan, ChinaDepartment of Breast and Thyroid Surgery, The Second Affiliated Hospital, Hainan Medical University, Haikou, Hainan, ChinaNHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan, ChinaNHC Key Laboratory of Tropical Disease Control, School of Tropical Medicine, Hainan Medical University, Haikou, Hainan, ChinaBackground Enhancing antigen cross-presentation is essential for the development of a tumor neoantigen vaccine. One approach is to stimulate antigen-presenting cells (APCs) to uptake neoantigens. Mycobacterium tuberculosis (MTb) contains pathogen-associated molecular patterns (PAMPs) recognized by APCs and adhesion molecules that facilitate MTb invasion of APCs. Therefore, we suggest using MTb as a carrier to enhance APC phagocytosis of neoantigens, thereby promoting antigen cross-presentation.Methods The successful preparation of the MTb carrier (phMTb) was confirmed through electron and confocal microscopy. Fluorescence microscopy was used to detect PAMPs and adhesion molecules on phMTb as well as to observe its role in aiding dendritic cells (DCs) in antigen uptake into endosomes or lysosomes. Flow cytometry was used to assess the retention of PAMPs and adhesion molecules on phMTb, investigate antigen uptake by DCs, evaluate their activation and maturation status, examine the presentation of tumor neoantigens, and analyze immune cells in draining lymph nodes and tumor tissues. The efficacy of phMTb vaccine formulations in combination with anti-programmed cell death protein 1 (PD-1) antibody therapy was assessed using the MC38 mouse tumor models. Adverse effects were evaluated through H&E staining of major organs, assessment of reproductive capability and detection of biochemical indices.Results The engineered porous hollow phMTb carrier successfully encapsulated model tumor neoantigens, with or without the adjuvant CpG. The phMTb retained PAMPs and adhesion molecules on its surface, similar to the parental MTb, thereby enhancing DC uptake of phMTb and its formulations containing tumor neoantigens and CpG. Vaccines formulated with phMTb facilitated DC maturation, activation, cross-presentation of tumor neoantigens, and promoted migration of phMTb-laden DCs to lymph nodes, enhancing effector and memory CD8+ T lymphocyte function. In murine tumor models, immunization with phMTb-formulated neoantigen vaccines elicited a robust tumor-specific cytotoxic T lymphocyte immune response with minimal adverse effects. Additionally, vaccination with phMTb-formulated neoantigen vaccines effectively reversed the tumor’s immune-suppressive microenvironment. Concurrent administration of the PD-1 antibody with the phMTb-formulated neoantigen vaccine exhibited significant synergistic therapeutic effects.Conclusions The results of our study highlight the potential clinical translation of personalized tumor neoantigen vaccines using the phMTb carrier.https://jitc.bmj.com/content/13/2/e010150.full |
| spellingShingle | Jie Jiang Feng-Ying Huang Shu-Zhen Dai Guang-Hong Tan Ming-Hui Chen Hengyu Chen Wu-Ping Zheng Ri-Hong Wu Weijing Xie Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens Journal for ImmunoTherapy of Cancer |
| title | Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens |
| title_full | Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens |
| title_fullStr | Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens |
| title_full_unstemmed | Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens |
| title_short | Reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens |
| title_sort | reinforcing cancer immunotherapy with engineered porous hollow mycobacterium tuberculosis loaded with tumor neoantigens |
| url | https://jitc.bmj.com/content/13/2/e010150.full |
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