Please wait a minute...

中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2022, Vol. 42 Issue (10): 39-50    DOI: 10.13523/j.cb.2204001
综述     
工程生物活药在肿瘤免疫治疗中的应用
韩春丽,王汉杰*()
天津大学生命科学学院 天津市微纳生物材料与检疗技术工程中心 天津市生物大分子结构功能与应用重点实验室 天津 30072
Advances of Engineered Live Biotherapeutics in Tumor Immunotherapy
Chun-li HAN,Han-jie WANG*()
School of Life Sciences, Tianjin University, Tianjin Engineering Center of Micro-Nano Biomaterials and Detection-Treatment Technology, Tianjin Key Laboratory of Function and Application of Biological Macromolecules,Tianjin 300072, China
 全文: PDF(1493 KB)   HTML
摘要：

人体细胞、细菌、病毒等生命体可以改造为工程生物活药,可在患者体内维持生物活性、自我复制并表达基因。相比于传统药物,工程生物活药在体内维持疗效时间长,具备外源基因表达能力,可实现多功能性和稳态调控,且具有独特的靶向、响应等能力。近年来,工程生物活药在肿瘤免疫治疗中的应用受到广泛关注,CAR-T等细胞治疗、溶瘤病毒疗法已在临床中获得良好的疗效,工程菌也在临床和临床前研究中发展迅猛。细胞、细菌、病毒三类活药的特性和治疗机制不同,因此具有不同的设计目的与思路。随着合成生物学技术的发展,工程生物活药将更安全、更高效,也将为肿瘤治疗带来新的机遇。针对工程生物活药在肿瘤免疫治疗中应用的最新进展开展了综述,阐述了不同生物活药的合成生物学设计和免疫治疗机制。
关键词： 生物活药;  合成生物学;  癌症免疫治疗    
Abstract:

Living organisms such as cells isolated from human body, bacteria, and viruses can be engineered as live biotherapeutics, which can maintain biological activity, self-replicate, and express genes in a patient’s body. Compared with traditional drugs, engineered live biotherapeutics maintain a relatively long-time curative effect in vivo, express genes as expected to achieve versatility and homeostasis control, and have unique targeting and response capabilities. In recent years, the application of engineered live biotherapeutics in tumor immunotherapy has received widespread attention. CAR-T and other cell therapies and oncolytic virus therapies have performed good clinical effects, and engineered bacteria are also developing rapidly in clinical and preclinical research. Among all the types of engineered live biotherapeutics, human cells, bacteria, and viruses have different characteristics. Therefore, their design purposes and ideas are different. With the progress of synthetic biology technologies, engineered live biotherapeutics will have better safety and efficacy, and bring new opportunities for tumor therapy. Herein, the latest developments of engineered live biotherapeutics for tumor immunotherapy are reviewed, and the synthetic biology design and immunotherapy mechanisms are expounded.
Key words: Live biotherapeutics    Synthetic biology    Tumor immunotherapy
收稿日期: 2022-04-01 出版日期: 2022-11-04
ZTFLH:  Q819  
通讯作者: 王汉杰     E-mail: wanghj@tju.edu.cn
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
韩春丽
王汉杰

引用本文:

韩春丽,王汉杰. 工程生物活药在肿瘤免疫治疗中的应用[J]. 中国生物工程杂志, 2022, 42(10): 39-50.

Chun-li HAN,Han-jie WANG. Advances of Engineered Live Biotherapeutics in Tumor Immunotherapy. China Biotechnology, 2022, 42(10): 39-50.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2204001    或    https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I10/39

图1  工程细胞活药的受体设计[8⇓-10]
商品名 抗原靶点 适用证 公司 批准年份
KYMRIAH CD19 复发或难治性急性淋巴细胞白血病 Novartis 2017
YESCARTA CD19 复发或难治性B细胞淋巴瘤 Kite Pharma Inc. 2018
TECARTUS CD19 复发或难治性套细胞淋巴瘤 Kite Pharma Inc. 2020
ABECMA BCMA 复发或难治性多发性骨髓瘤 BMS 2021
BREYANZI CD19 复发或难治性B细胞淋巴瘤 BMS 2021
瑞基奥仑赛注射液 CD19 复发或难治性B细胞淋巴瘤 药明巨诺 2021
CARVYKTI BCMA 复发或难治性多发性骨髓瘤 传奇生物 2022
表1  已获批的CAR-T工程细胞活药
图2  溶瘤病毒活药发挥作用的三个环节
商品名 适用证 公司 批准机构 批准年份
Rigvir 黑色素瘤 Latima 拉脱维亚药品管理署 2004
安柯瑞 晚期鼻咽癌 上海三维 中国国家食品药品监督管理总局 2005
Imlygic(T-Vec) 黑色素瘤 Kite Pharma Inc. 美国食品药品监督管理局 2015
Delytact 恶性胶质瘤 传奇生物 日本厚生劳动省 2021
表2  已获批的溶瘤病毒活药
图3  工程菌活药的基因回路设计
底盘类型 商品名 适用证 公司 临床试验段
大肠杆菌 SYNB1891 转移性实体瘤、淋巴瘤 Synlogic I期
VAX014 膀胱移行细胞癌 Vaxiion I期
沙门氏菌 VNP20009 实体瘤、转移瘤 Vion Pharma. I期
VXM01 复发性胶质母细胞瘤 Vaximm GmbH I/II期
双歧杆菌 APS001F 实体瘤 Anaeropharma Science I/II期
EDP1503 复发性结直肠癌 Evelo Biosciences I/II期
李斯特菌 ADXS31-142 前列腺癌 Advaxis I/II期
CRS-207 胰腺癌 约翰霍普金斯大学 II期
表3  用于肿瘤免疫治疗的工程菌活药临床试验
[1] Ozdemir T, Fedorec A J H, Danino T, et al. Synthetic biology and engineered live biotherapeutics: toward increasing system complexity. Cell Systems, 2018, 7(1): 5-16.
doi: S2405-4712(18)30248-5 pmid: 30048620
[2] Cubillos-Ruiz A, Guo T X, Sokolovska A, et al. Engineering living therapeutics with synthetic biology. Nature Reviews Drug Discovery, 2021, 20(12): 941-960.
doi: 10.1038/s41573-021-00285-3 pmid: 34616030
[3] Kitada T, DiAndreth B, Teague B, et al. Programming gene and engineered-cell therapies with synthetic biology. Science, 2018, 359(6376): eaad1067.
[4] Monie D D, Bhandarkar A R, Parney I F, et al. Synthetic and systems biology principles in the design of programmable oncolytic virus immunotherapies for glioblastoma. Neurosurgical Focus, 2021, 50(2): E10.
doi: 10.3171/2020.12.FOCUS20855 pmid: 33524942
[5] Hong M H, Clubb J D, Chen Y Y. Engineering CAR-T cells for next-generation cancer therapy. Cancer Cell, 2020, 38(4): 473-488.
doi: 10.1016/j.ccell.2020.07.005 pmid: 32735779
[6] Sieow B F L, Wun K S, Yong W P, et al. Tweak to treat: reprograming bacteria for cancer treatment. Trends in Cancer, 2021, 7(5): 447-464.
doi: 10.1016/j.trecan.2020.11.004 pmid: 33303401
[7] Fukuhara H, Ino Y, Todo T. Oncolytic virus therapy: a new era of cancer treatment at dawn. Cancer Science, 2016, 107(10): 1373-1379.
doi: 10.1111/cas.13027 pmid: 27486853
[8] Zhang C, Liu J, Zhong J F, et al. Engineering CAR-T cells. Biomarker Research, 2017, 5: 22.
doi: 10.1186/s40364-017-0102-y pmid: 28652918
[9] Liu Y, Liu G N, Wang J S, et al. Chimeric STAR receptors using TCR machinery mediate robust responses against solid tumors. Science Translational Medicine, 2021, 13(586): eabb5191.
[10] Morsut L, Roybal K T, Xiong X, et al. Engineering customized cell sensing and response behaviors using synthetic Notch receptors. Cell, 2016, 164(4): 780-791.
doi: 10.1016/j.cell.2016.01.012 pmid: 26830878
[11] Abramson J S. Anti-CD19 CAR T-cell therapy for B-cell non-Hodgkin lymphoma. Transfusion Medicine Reviews, 2020, 34(1): 29-33.
doi: S0887-7963(19)30076-8 pmid: 31677848
[12] Mikkilineni L, Kochenderfer J N. CAR T cell therapies for patients with multiple myeloma. Nature Reviews Clinical Oncology, 2021, 18(2): 71-84.
doi: 10.1038/s41571-020-0427-6
[13] Acuto O, Michel F. CD28-mediated co-stimulation: a quantitative support for TCR signalling. Nature Reviews Immunology, 2003, 3(12): 939-951.
doi: 10.1038/nri1248 pmid: 14647476
[14] Ramos C A, Rouce R, Robertson C S, et al. In vivo fate and activity of second- versus third-generation CD19-specific CAR-T cells in B cell non-Hodgkin’s lymphomas. Molecular Therapy, 2018, 26(12): 2727-2737.
doi: 10.1016/j.ymthe.2018.09.009
[15] Roselli E, Faramand R, Davila M L. Insight into next-generation CAR therapeutics: designing CAR T cells to improve clinical outcomes. The Journal of Clinical Investigation, 2021, 131(2): e142030.
[16] Chmielewski M, Hombach A A, Abken H. Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. Immunological Reviews, 2014, 257(1): 83-90.
doi: 10.1111/imr.12125 pmid: 24329791
[17] Chmielewski M, Abken H. CAR T cells releasing IL-18 convert to T-bethigh FoxO1low effectors that exhibit augmented activity against advanced solid tumors. Cell Reports, 2017, 21(11): 3205-3219.
doi: S2211-1247(17)31715-1 pmid: 29241547
[18] Kagoya Y, Tanaka S, Guo T X, et al. A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects. Nature Medicine, 2018, 24(3): 352-359.
doi: 10.1038/nm.4478 pmid: 29400710
[19] Zhao Q J, Jiang Y, Xiang S X, et al. Engineered TCR-T cell immunotherapy in anticancer precision medicine: pros and cons. Frontiers in Immunology, 2021, 12: 658753.
doi: 10.3389/fimmu.2021.658753
[20] Stone J D, Harris D T, Soto C M, et al. A novel T cell receptor single-chain signaling complex mediates antigen-specific T cell activity and tumor control. Cancer Immunology, Immunotherapy: CII, 2014, 63(11): 1163-1176.
[21] Segaliny A I, Li G D, Kong L S, et al. Functional TCR T cell screening using single-cell droplet microfluidics. Lab on a Chip, 2018, 18(24): 3733-3749.
doi: 10.1039/c8lc00818c pmid: 30397689
[22] Zhao X, Kolawole E M, Chan W P, et al. Tuning T cell receptor sensitivity through catch bond engineering. Science, 2022, 376(6589): eabl5282.
[23] Xia M, Chen J H, Meng G, et al. CXCL10 encoding synNotch T cells enhance anti-tumor immune responses without systemic side effect. Biochemical and Biophysical Research Communications, 2021, 534: 765-772.
doi: 10.1016/j.bbrc.2020.11.002 pmid: 33213838
[24] Choe J H, Watchmaker P B, Simic M S, et al. SynNotch-CAR T cells overcome challenges of specificity, heterogeneity, and persistence in treating glioblastoma. Science Translational Medicine, 2021, 13(591): eabe7378.
[25] Zheng Y, Nandakumar K S, Cheng K. Optimization of CAR-T cell-based therapies using small-molecule-based safety switches. Journal of Medicinal Chemistry, 2021, 64(14): 9577-9591.
doi: 10.1021/acs.jmedchem.0c02054
[26] Sakemura R, Terakura S, Watanabe K, et al. A Tet-on inducible system for controlling CD19-chimeric antigen receptor expression upon drug administration. Cancer Immunology Research, 2016, 4(8): 658-668.
doi: 10.1158/2326-6066.CIR-16-0043 pmid: 27329987
[27] Yang L F, Yin J L, Wu J L, et al. Engineering genetic devices for in vivo control of therapeutic T cell activity triggered by the dietary molecule resveratrol. Proceedings of the National Academy of Sciences of the United States of America, 2021, 118(34): e2106612118.
[28] Leung W H, Gay J, Martin U, et al. Sensitive and adaptable pharmacological control of CAR T cells through extracellular receptor dimerization. JCI Insight, 2019, 5(11): e124430.
[29] Nguyen N T, Huang K, Zeng H X, et al. Nano-optogenetic engineering of CAR T cells for precision immunotherapy with enhanced safety. Nature Nanotechnology, 2021, 16(12): 1424-1434.
doi: 10.1038/s41565-021-00982-5 pmid: 34697491
[30] Xie G Z, Dong H, Liang Y, et al. CAR-NK cells: a promising cellular immunotherapy for cancer. eBioMedicine, 2020, 59: 102975.
[31] Ueda T, Kumagai A, Iriguchi S, et al. Non-clinical efficacy, safety and stable clinical cell processing of induced pluripotent stem cell-derived anti-glypican-3 chimeric antigen receptor-expressing natural killer/innate lymphoid cells. Cancer Science, 2020, 111(5): 1478-1490.
doi: 10.1111/cas.14374 pmid: 32133731
[32] Kriegsmann K, Kriegsmann M, von Bergwelt-Baildon M, et al. NKT cells: new players in CAR cell immunotherapy? European Journal of Haematology, 2018, 101(6): 750-757.
doi: 10.1111/ejh.13170 pmid: 30187578
[33] Chen Y Z, Yu Z Y, Tan X W, et al. CAR-macrophage: a new immunotherapy candidate against solid tumors. Biomedicine & Pharmacotherapy, 2021, 139: 111605.
doi: 10.1016/j.biopha.2021.111605
[34] Klichinsky M, Ruella M, Shestova O, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nature Biotechnology, 2020, 38(8): 947-953.
doi: 10.1038/s41587-020-0462-y pmid: 32361713
[35] Morrissey M A, Williamson A P, Steinbach A M, et al. Chimeric antigen receptors that trigger phagocytosis. eLife, 2018, 7: e36688.
[36] Han D L, Xu Z H, Zhuang Y, et al. Current progress in CAR-T cell therapy for hematological malignancies. Journal of Cancer, 2021, 12(2): 326-334.
doi: 10.7150/jca.48976 pmid: 33391429
[37] Liang Q, Monetti C, Shutova M V, et al. Linking a cell-division gene and a suicide gene to define and improve cell therapy safety. Nature, 2018, 563(7733): 701-704.
doi: 10.1038/s41586-018-0733-7
[38] Di Stasi A, Tey S K, Dotti G, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med, 2011, 365(18): 1673-1683.
doi: 10.1056/NEJMoa1106152
[39] Glover M, Avraamides S, Maher J. How can we engineer CAR T cells to overcome resistance? Biologics: Targets & Therapy, 2021, 15: 175-198.
[40] Delgoffe G M, Xu C Q, Mackall C L, et al. The role of exhaustion in CAR T cell therapy. Cancer Cell, 2021, 39(7): 885-888.
doi: 10.1016/j.ccell.2021.06.012 pmid: 34256903
[41] Han X, Wang Y, Wei J S, et al. Multi-antigen-targeted chimeric antigen receptor T cells for cancer therapy. Journal of Hematology & Oncology, 2019, 12(1): 128.
[42] Kirtane K, Elmariah H, Chung C H, et al. Adoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead. Journal for Immunotherapy of Cancer, 2021, 9(7): e002723.
[43] Bommareddy P K, Patel A, Hossain S, et al. Talimogene laherparepvec (T-VEC) and other oncolytic viruses for the treatment of melanoma. American Journal of Clinical Dermatology, 2017, 18(1): 1-15.
doi: 10.1007/s40257-016-0238-9 pmid: 27988837
[44] Deng L L, Fan J, Ding Y D, et al. Oncolytic cancer therapy with a vaccinia virus strain. Oncology Reports, 2019, 41(1): 686-692.
doi: 10.3892/or.2018.6801 pmid: 30365140
[45] Garcia-Moure M, Martinez-Vélez N, Patiño-García A, et al. Oncolytic adenoviruses as a therapeutic approach for osteosarcoma: a new hope. Journal of Bone Oncology, 2016, 9: 41-47.
doi: 10.1016/j.jbo.2016.12.001
[46] Kaufman H L, Kohlhapp F J, Zloza A. Oncolytic viruses: a new class of immunotherapy drugs. Nature Reviews Drug Discovery, 2015, 14(9): 642-662.
doi: 10.1038/nrd4663 pmid: 26323545
[47] Zainutdinov S S, Kochneva G V, Netesov S V, et al. Directed evolution as a tool for the selection of oncolytic RNA viruses with desired phenotypes. Oncolytic Virotherapy, 2019, 8: 9-26.
doi: 10.2147/OV.S176523 pmid: 31372363
[48] Schneider U, Bullough F, Vongpunsawad S, et al. Recombinant measles viruses efficiently entering cells through targeted receptors. Journal of Virology, 2000, 74(21): 9928-9936.
pmid: 11024120
[49] Nakamura T, Peng K W, Harvey M, et al. Rescue and propagation of fully retargeted oncolytic measles viruses. Nature Biotechnology, 2005, 23(2): 209-214.
doi: 10.1038/nbt1060 pmid: 15685166
[50] Springfeld C, von Messling V, Frenzke M, et al. Oncolytic efficacy and enhanced safety of measles virus activated by tumor-secreted matrix metalloproteinases. Cancer Research, 2006, 66(15): 7694-7700.
pmid: 16885371
[51] Choi J W, Lee J S, Kim S W, et al. Evolution of oncolytic adenovirus for cancer treatment. Advanced Drug Delivery Reviews, 2012, 64(8): 720-729.
doi: 10.1016/j.addr.2011.12.011
[52] Ahmed M, McKenzie M O, Puckett S, et al. Ability of the matrix protein of vesicular stomatitis virus to suppress beta interferon gene expression is genetically correlated with the inhibition of host RNA and protein synthesis. Journal of Virology, 2003, 77(8): 4646-4657.
pmid: 12663771
[53] Bischoff J R, Kirn D H, Williams A, et al. An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science, 1996, 274(5286): 373-376.
doi: 10.1126/science.274.5286.373 pmid: 8832876
[54] Ruiz A J, Russell S J. microRNAs and oncolytic viruses. Current Opinion in Virology, 2015, 13: 40-48.
doi: 10.1016/j.coviro.2015.03.007 pmid: 25863717
[55] Huang H Y, Liu Y Q, Liao W X, et al. Oncolytic adenovirus programmed by synthetic gene circuit for cancer immunotherapy. Nature Communications, 2019, 10: 4801.
doi: 10.1038/s41467-019-12794-2 pmid: 31641136
[56] Miller A, Suksanpaisan L, Naik S, et al. Reporter gene imaging identifies intratumoral infection voids as a critical barrier to systemic oncolytic virus efficacy. Molecular Therapy - Oncolytics, 2014, 1: 14005.
doi: 10.1038/mto.2014.5
[57] Mato-Berciano A, Morgado S, Maliandi M V, et al. Oncolytic adenovirus with hyaluronidase activity that evades neutralizing antibodies: VCN-11. Journal of Controlled Release, 2021, 332: 517-528.
doi: 10.1016/j.jconrel.2021.02.035 pmid: 33675877
[58] Kiyokawa J, Kawamura Y, Ghouse S M, et al. Modification of extracellular matrix enhances oncolytic adenovirus immunotherapy in glioblastoma. Clinical Cancer Research: an Official Journal of the American Association for Cancer Research, 2021, 27(3): 889-902.
doi: 10.1158/1078-0432.CCR-20-2400
[59] Kaufman H L, Ruby C E, Hughes T, et al. Current status of granulocyte-macrophage colony-stimulating factor in the immunotherapy of melanoma. Journal for Immunotherapy of Cancer, 2014, 2: 11.
doi: 10.1186/2051-1426-2-11 pmid: 24971166
[60] Bommareddy P K, Shettigar M, Kaufman H L. Integrating oncolytic viruses in combination cancer immunotherapy. Nature Reviews Immunology, 2018, 18(8): 498-513.
doi: 10.1038/s41577-018-0014-6 pmid: 29743717
[61] Park A K, Fong Y, Kim S I, et al. Effective combination immunotherapy using oncolytic viruses to deliver CAR targets to solid tumors. Science Translational Medicine, 2020, 12(559): eaaz1863.
[62] Tan G W, Kasuya H, Sahin T T, et al. Combination therapy of oncolytic Herpes simplex virus HF10 and bevacizumab against experimental model of human breast carcinoma xenograft. International Journal of Cancer, 2015, 136(7): 1718-1730.
doi: 10.1002/ijc.29163
[63] Hu P Y, Fan X M, Zhang Y N, et al. The limiting factors of oncolytic virus immunotherapy and the approaches to overcome them. Applied Microbiology and Biotechnology, 2020, 104(19): 8231-8242.
doi: 10.1007/s00253-020-10802-w
[64] Martin N T, Bell J C. Oncolytic virus combination therapy: killing one bird with two stones. Molecular Therapy, 2018, 26(6): 1414-1422.
doi: S1525-0016(18)30158-8 pmid: 29703699
[65] Hamada M, Yura Y. Efficient delivery and replication of oncolytic virus for successful treatment of head and neck cancer. International Journal of Molecular Sciences, 2020, 21(19): 7073.
doi: 10.3390/ijms21197073
[66] Forbes N S. Engineering the perfect (bacterial) cancer therapy. Nature Reviews Cancer, 2010, 10(11): 785-794.
doi: 10.1038/nrc2934 pmid: 20944664
[67] Lee C H, Wu C L, Shiau A L. Salmonella choleraesuis as an anticancer agent in a syngeneic model of orthotopic hepatocellular carcinoma. International Journal of Cancer, 2008, 122(4): 930-935.
doi: 10.1002/ijc.23047
[68] Lynch J P, Goers L, Lesser C F. Emerging strategies for engineering Escherichia coli Nissle 1917-based therapeutics. Trends in Pharmacological Sciences, 2022, 43(9): 772-786.
doi: 10.1016/j.tips.2022.02.002
[69] Dang L H, Bettegowda C, Huso D L, et al. Combination bacteriolytic therapy for the treatment of experimental tumors. Proceedings of the National Academy of Sciences of the United States of America, 2001, 98(26): 15155-15160.
[70] Kurtz C B, Millet Y A, Puurunen M K, et al. An engineered E. coli Nissle improves hyperammonemia and survival in mice and shows dose-dependent exposure in healthy humans. Science Translational Medicine, 2019, 11(475): eaau7975.
[71] Brophy J A N, Voigt C A. Principles of genetic circuit design. Nature Methods, 2014, 11(5): 508-520.
doi: 10.1038/nmeth.2926 pmid: 24781324
[72] Chien T, Harimoto T, Kepecs B, et al. Enhancing the tropism of bacteria via genetically programmed biosensors. Nature Biomedical Engineering, 2022, 6(1): 94-104.
doi: 10.1038/s41551-021-00772-3
[73] Loessner H, Endmann A, Leschner S, et al. Remote control of tumour-targeted Salmonella enterica serovar typhimurium by the use of l-arabinose as inducer of bacterial gene expression in vivo. Cellular Microbiology, 2007, 9(6): 1529-1537.
pmid: 17298393
[74] Royo J L, Becker P D, Camacho E M, et al. In vivo gene regulation in Salmonella spp. by a salicylate-dependent control circuit. Nature Methods, 2007, 4(11): 937-942.
doi: 10.1038/nmeth1107
[75] Fernandez-Rodriguez J, Moser F, Song M, et al. Engineering RGB color vision into Escherichia coli. Nature Chemical Biology, 2017, 13(7): 706-708.
doi: 10.1038/nchembio.2390 pmid: 28530708
[76] Pan H Z, Li L Y, Pang G J, et al. Engineered NIR light-responsive bacteria as anti-tumor agent for targeted and precise cancer therapy. Chemical Engineering Journal, 2021, 426: 130842.
doi: 10.1016/j.cej.2021.130842
[77] Abedi M H, Yao M S, Mittelstein D R, et al. Ultrasound-controllable engineered bacteria for cancer immunotherapy. Nature Communications, 2022, 13: 1585.
doi: 10.1038/s41467-022-29065-2 pmid: 35332124
[78] Nuyts S, van Mellaert L, Barbé S, et al. Insertion or deletion of the Cheo box modifies radiation inducibility of Clostridium promoters. Applied and Environmental Microbiology, 2001, 67(10): 4464-4470.
doi: 10.1128/AEM.67.10.4464-4470.2001 pmid: 11571144
[79] Anderson J C, Voigt C A, Arkin A P. Environmental signal integration by a modular AND gate. Molecular Systems Biology, 2007, 3: 133.
pmid: 17700541
[80] Nielsen A A K, Der B S, Shin J, et al. Genetic circuit design automation. Science, 2016, 352(6281): aac7341.
[81] Montaño López J, Duran L, Avalos J L. Physiological limitations and opportunities in microbial metabolic engineering. Nature Reviews Microbiology, 2022, 20(1): 35-48.
doi: 10.1038/s41579-021-00600-0
[82] Freudl R. Signal peptides for recombinant protein secretion in bacterial expression systems. Microbial Cell Factories, 2018, 17(1): 52.
doi: 10.1186/s12934-018-0901-3 pmid: 29598818
[83] Löfblom J. Bacterial display in combinatorial protein engineering. Biotechnology Journal, 2011, 6(9): 1115-1129.
doi: 10.1002/biot.201100129 pmid: 21786423
[84] Ho C L, Tan H Q, Chua K J, et al. Engineered commensal microbes for diet-mediated colorectal-cancer chemoprevention. Nature Biomedical Engineering, 2018, 2(1): 27-37.
doi: 10.1038/s41551-017-0181-y pmid: 31015663
[85] Din M O, Danino T, Prindle A, et al. Synchronized cycles of bacterial lysis for in vivo delivery. Nature, 2016, 536(7614): 81-85.
doi: 10.1038/nature18930
[86] Tan W Z, Duong M T Q, Zuo C H, et al. Targeting of pancreatic cancer cells and stromal cells using engineered oncolytic Salmonella typhimurium. Molecular Therapy, 2022, 30(2): 662-671.
doi: 10.1016/j.ymthe.2021.08.023
[87] Fan J X, Li Z H, Liu X H, et al. Bacteria-mediated tumor therapy utilizing photothermally-controlled TNF-α expression via oral administration. Nano Lett, 2018, 18(4): 2373-2380.
doi: 10.1021/acs.nanolett.7b05323
[88] Gurbatri C R, Lia I, Vincent R, et al. Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies. Science Translational Medicine, 2020, 12(530): eaax0876.
[89] Gentschev I, Fensterle J, Schmidt A, et al. Use of a recombinant Salmonella enterica serovar typhimurium strain expressing C-Raf for protection against C-Raf induced lung adenoma in mice. BMC Cancer, 2005, 5: 15.
pmid: 15703070
[90] Fensterle J, Bergmann B, Yone C L R P, et al. Cancer immunotherapy based on recombinant Salmonella enterica serovar typhimurium AroA strains secreting prostate-specific antigen and cholera toxin subunit B. Cancer Gene Therapy, 2008, 15(2): 85-93.
pmid: 18084243
[91] Canale F P, Basso C, Antonini G, et al. Metabolic modulation of tumours with engineered bacteria for immunotherapy. Nature, 2021, 598(7882): 662-666.
doi: 10.1038/s41586-021-04003-2
[92] Griffin M E, Espinosa J, Becker J L, et al. Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy. Science, 2021, 373(6558): 1040-1046.
doi: 10.1126/science.abc9113
[93] Chan C T Y, Lee J W, Cameron D E, et al. ‘Deadman’ and ‘Passcode’ microbial kill switches for bacterial containment. Nature Chemical Biology, 2016, 12(2): 82-86.
doi: 10.1038/nchembio.1979
[94] Piñero-Lambea C, Bodelón G, Fernández-Periáñez R, et al. Programming controlled adhesion of E. coli to target surfaces, cells, and tumors with synthetic adhesins. ACS Synthetic Biology, 2015, 4(4): 463-473.
doi: 10.1021/sb500252a pmid: 25045780
[95] Harimoto T, Hahn J, Chen Y Y, et al. A programmable encapsulation system improves delivery of therapeutic bacteria in mice. Nature Biotechnology, 2022, 40(8): 1259-1269.
doi: 10.1038/s41587-022-01244-y
[96] Centurion F, Basit A W, Liu J Y, et al. Nanoencapsulation for probiotic delivery. ACS Nano, 2021, 15(12): 18653-18660.
doi: 10.1021/acsnano.1c09951 pmid: 34860008
[97] Cao Z P, Cheng S S, Wang X Y, et al. Camouflaging bacteria by wrapping with cell membranes. Nature Communications, 2019, 10: 3452.
doi: 10.1038/s41467-019-11390-8 pmid: 31388002
[98] Bacchus W, Aubel D, Fussenegger M. Biomedically relevant circuit-design strategies in mammalian synthetic biology. Molecular Systems Biology, 2013, 9: 691.
doi: 10.1038/msb.2013.48 pmid: 24061539
[99] Guedan S, Calderon H, Posey A D Jr, et al. Engineering and design of chimeric antigen receptors. Molecular Therapy - Methods & Clinical Development, 2019, 12: 145-156.
[1] 曾雪霞,但玉,毛绍名,孙佳慧,栾国栋,吕雪峰. 蓝藻光驱固碳合成糖类物质的技术研究进展*[J]. 中国生物工程杂志, 2022, 42(7): 90-100.
[2] 张大璐,葛奇,冯一博,陈为刚. DNA数据存储的科研概况国际对比与分析[J]. 中国生物工程杂志, 2022, 42(6): 116-129.
[3] 白松,侯正杰,高庚荣,乔斌,程景胜. 微生物合成奇数链脂肪酸研究进展*[J]. 中国生物工程杂志, 2022, 42(6): 76-85.
[4] 梁世玉,万里,郭潇佳,王雪颖,吕力婷,胡英菡,赵宗保. 构建可合成非天然辅酶的圆红冬孢酵母工程菌*[J]. 中国生物工程杂志, 2022, 42(5): 58-68.
[5] 李慧敏,贾斌,李霞,刘夺. 合成芳香族化合物的酵母底盘改造策略*[J]. 中国生物工程杂志, 2022, 42(10): 80-92.
[6] 马宁,王汉杰. 光遗传学在细菌生产调控中的应用进展[J]. 中国生物工程杂志, 2021, 41(9): 101-109.
[7] 黄焕邦,吴洋,杨友辉,王兆官,齐浩. 基于古菌酪氨酰tRNA合成酶非天然氨基酸插入的研究进展[J]. 中国生物工程杂志, 2021, 41(9): 110-125.
[8] 郭曼曼,田开仁,乔建军,李艳妮. 噬菌体重组酶系统在合成生物学中的应用*[J]. 中国生物工程杂志, 2021, 41(8): 90-102.
[9] 董曙馨,秦磊,李春,李珺. 利用转录因子工程重塑代谢网络实现细胞工厂高效生产[J]. 中国生物工程杂志, 2021, 41(4): 55-63.
[10] 郑义,郭世英,隋凤翔,杨骐羽,卫雅萱,李晓岩. 群体感应系统在合成生物学中的应用*[J]. 中国生物工程杂志, 2021, 41(11): 100-109.
[11] 察亚平, 朱牧孜, 李爽. 体内连续定向进化研究进展 *[J]. 中国生物工程杂志, 2021, 41(1): 42-51.
[12] 郭二鹏, 张建志, 司同. 羊毛硫肽的高通量工程改造方法新进展 *[J]. 中国生物工程杂志, 2021, 41(1): 30-41.
[13] 常璐, 黄娇芳, 董浩, 周斌辉, 朱小娟, 庄英萍. 合成生物学改造微生物及生物被膜用于重金属污染检测与修复 *[J]. 中国生物工程杂志, 2021, 41(1): 62-71.
[14] 饶海密,梁冬梅,李伟国,乔建军,财音青格乐. 真菌芳香聚酮化合物的合成生物学研究进展*[J]. 中国生物工程杂志, 2020, 40(9): 52-61.
[15] 张玉婷,李伟国,梁冬梅,乔建军,财音青格乐. P450s在萜类合成方面的合成生物学研究进展 *[J]. 中国生物工程杂志, 2020, 40(8): 84-96.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会