Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin

Science Translational Medicine

Volumn 9, Issue 376, 2017, Pages

  Zheng, Jin Hai ^a,b   Nguyen, Vu H ^a,c   Jiang, Sheng Nan ^d,e   Park, Seung Hwan ^f   Tan, Wenzhi ^d   Hong, Seol Hee ^b   Shin, Myung Geun ^d   Chung, Ik Joo ^d   Hong, Yeongjin ^d   Bom, Hee Seung ^d   Choy, Hyon E ^b,d   Lee, Shee Eun ^b   Rhee, Joon Haeng ^b,d   Min, Jung Joon ^a,b,d  

^a Chonnam National University Research Institute of Medical Sciences   (South Korea)

^b Chonnam National University   (South Korea)

^c CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^d Chonnam National University Medical School   (South Korea)

^e CENTRAL SOUTH UNIVERSITY   (China)

^f Korea Research Institute of Bioscience and Biotechnology (KRIBB)   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

FLAGELLIN; FLAGELLIN B; MYELOID DIFFERENTIATION FACTOR 88; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 5; UNCLASSIFIED DRUG; FLAB FLAGELLIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BACTERIAL COLONIZATION; CANCER CELL LINE; CANCER IMMUNOTHERAPY; CANCER INHIBITION; CELL INFILTRATION; COLON CANCER; COLON CANCER CELL LINE; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN CELL; MACROPHAGE; MALE; METASTASIS INHIBITION; MONOCYTE; MOUSE; NEUTROPHIL; NONHUMAN; SALMONELLA ENTERICA SEROVAR TYPHIMURIUM; SURVIVAL TIME; TUMOR ASSOCIATED LEUKOCYTE; TUMOR MICROENVIRONMENT; TUMOR REGRESSION; VIBRIO VULNIFICUS; ANIMAL; BACTERIAL COUNT; C57BL MOUSE; CELL POLARITY; COLON TUMOR; DRUG SCREENING; GENETIC ENGINEERING; HCT 116 CELL LINE; IMMUNOLOGY; IMMUNOTHERAPY; METABOLISM; METASTASIS; NEOPLASM; NUDE MOUSE; PATHOLOGY; PHENOTYPE; PHYSIOLOGY; SECRETION (PROCESS); SIGNAL TRANSDUCTION;

ANIMALS; CELL POLARITY; COLONIC NEOPLASMS; COLONY COUNT, MICROBIAL; FLAGELLIN; GENETIC ENGINEERING; HCT116 CELLS; HUMANS; IMMUNOTHERAPY; MACROPHAGES; MALE; MICE, INBRED C57BL; MICE, NUDE; NEOPLASM METASTASIS; NEOPLASMS; PHENOTYPE; SALMONELLA TYPHIMURIUM; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 5; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85012934976     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aak9537     Document Type: Article

References (52)

1. W. Wei, Q. H. Shi, F. Remacle, L. D. Qin, D. B. Shackelford, Y. S. Shin, P. S. Mischel, R. D. Levine, J. R. Heath, Hypoxia induces a phase transition within a kinase signaling network in cancer cells. Proc. Natl. Acad. Sci. U.S.A. 110, E1352-E1360 (2013).
2. J. M. Brown, W. R. William, Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer 4, 437-447 (2004).
3. H. Zhu, Z. Li, S. Mao, B. Ma, S. Zhou, L. Deng, T. Liu, D. Cui, Y. Zhao, J. He, C. Yi, Y. Huang, Antitumor effect of sFlt-1 gene therapy system mediated by Bifidobacterium Infantis on Lewis lung cancer in mice. Cancer Gene Ther. 18, 884-896 (2011).
4. M. Zhao, M. Yang, X. M. Li, P. Jiang, E. Baranov, S. Li, M. Xu, S. Penman, R. M. Hoffman, Tumor-Targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium. Proc. Natl. Acad. Sci. U.S.A. 102, 755-760 (2005).
5. S. N. Jiang, S. H. Park, H. J. Lee, J. H. Zheng, H. S. Kim, H. S. Bom, Y. Hong, M. Szardenings, M. G. Shin, S. C. Kim, V. Ntziachristos, H. E. Choy, J. J. Min, Engineering of bacteria for the visualization of targeted delivery of a cytolytic anticancer agent. Mol. Ther. 21, 1985-1995 (2013).
6. J.-J. Min, V. H. Nguyen, H.-J. Kim, Y. Hong, H. E. Choy, Quantitative bioluminescence imaging of tumor-Targeting bacteria in living animals. Nat. Protoc. 3, 629-636 (2008).
7. S. N. Jiang, T. X. Phan, T. K. Nam, V. H. Nguyen, H. S. Kim, H. S. Bom, H. E. Choy, Y. Hong, J.-J. Min, Inhibition of tumor growth and metastasis by a combination of Escherichia coli-mediated cytolytic therapy and radiotherapy. Mol. Ther. 18, 635-642 (2010).
8. N. J. Roberts, L. Zhang, F. Janku, A. Collins, R.-Y. Bai, V. Staedtke, A. W. Rusk, D. Tung, M. Miller, J. Roix, K. V. Khanna, R. Murthy, R. S. Benjamin, T. Helgason, A. D. Szvalb, J. E. Bird, S. Roy-Chowdhuri, H. H. Zhang, Y. Qiao, B. Karim, J. McDaniel, A. Elpiner, A. Sahora, J. Lachowicz, B. Phillips, A. Turner, M. K. Klein, G. Post, L. A. Diaz Jr., G. J. Riggins, N. Papadopoulos, K. W. Kinzler, B. Vogelstein, C. Bettegowda, D. L. Huso, M. Varterasian, S. Saha, S. Zhou, Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. Sci. Transl. Med. 6, 249ra111 (2014).
9. D. Akin, J. Sturgis, K. Ragheb, D. Sherman, K. Burkholder, J. P. Robinson, A. K. Bhunia, S. Mohammed, R. Bashir, Bacteria-mediated delivery of nanoparticles and cargo into cells. Nat. Nanotechnol. 2, 441-449 (2007).
10. C. Clairmont, K. C. Lee, J. Pike, M. Ittensohn, K. B. Low, J. Pawelek, D. Bermudes, S. M. Brecher, D. Margitich, J. Turnier, Z. Li, X. Luo, I. King, L. M. Zheng, Biodistribution and genetic stability of the novel antitumor agent VNP20009, a genetically modified strain of Salmonella typhimurium. J. Infect. Dis. 181, 1996-2002 (2000).
11. P. Chorobik, D. Czaplicki, K. Ossysek, J. Bereta, Salmonella and cancer: From pathogens to therapeutics. Acta Biochim. Pol. 60, 285-297 (2013).
12. J. F. Toso, V. J. Gill, P. Hwu, F. M. Marincola, N. P. Restifo, D. J. Schwartzentruber, R. M. Sherry, S. L. Topalian, J. C. Yang, F. Stock, L. J. Freezer, K. E. Morton, C. Seipp, L. Haworth, S. Mavroukakis, D. White, S. MacDonald, J. Mao, M. Sznol, S. A. Rosenberg, Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. J. Clin. Oncol. 20, 142-152 (2002).
13. C. Yam, M. Zhao, K. Hayashi, H. Y. Ma, H. Kishimoto, M. McElroy, M. Bouvet, R. M. Hoffman, Monotherapy with a tumor-Targeting mutant of S. typhimurium Inhibits liver metastasis in a mouse model of pancreatic cancer. J. Surg. Res. 164, 248-255 (2010).
14. M. Zhao, M. Yang, H. Y. Ma, X. M. Li, X. Y. Tan, S. K. Li, Z. J. Yang, R. M. Hoffman, Targeted therapy with a Salmonella typhimurium leucine-Arginine auxotroph cures orthotopic human breast tumors in nude mice. Cancer Res. 66, 7647-7652 (2006).
15. M. Zhao, J. Geller, H. Ma, M. Yang, S. Penman, R. M. Hoffman, Monotherapy with a tumor-Targeting mutant of Salmonella typhimurium cures orthotopic metastatic mouse models of human prostate cancer. Proc. Natl. Acad. Sci. U.S.A. 104, 10170-10174 (2007).
16. S. Yano, Y. Zhang, M. Zhao, Y. Hiroshima, S. Miwa, F. Uehara, H. Kishimoto, H. Tazawa, M. Bouvet, T. Fujiwara, R. M. Hoffman, Tumor-Targeting Salmonella typhimurium A1-R decoys quiescent cancer cells to cycle as visualized by FUCCI imaging and become sensitive to chemotherapy. Cell Cycle 13, 3958-3963 (2014).
17. H. S. Na, H. J. Kim, H.-C. Lee, Y. Hong, J. H. Rhee, H. E. Choy, Immune response induced by Salmonella typhimurium defective in ppGpp synthesis. Vaccine 24, 2027-2034 (2006).
18. V. H. Nguyen, H.-S. Kim, J.-M. Ha, Y. J. Hong, H. E. Choy, J.-J. Min, Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer. Cancer Res. 70, 18-23 (2010).
19. J.-H. Jeong, K. Kim, D. Lim, K. Jeong, Y. Hong, V. H. Nguyen, T.-H. Kim, S. Ryu, J.-A. Lim, J. I. Kim, G.-J. Kim, S. C. Kim, J.-J. Min, H. E. Choy, Anti-Tumoral effect of the mitochondrial target domain of Noxa delivered by an engineered Salmonella typhimurium. PLOS ONE 9, e80050 (2014).
20. M. Loeffler, G. Le'Negrate, M. Krajewska, J. C. Reed, IL-18-producing Salmonella inhibit tumor growth. Cancer Gene Ther. 15, 787-794 (2008).
21. H. Nishikawa, E. Sato, G. Briones, L.-M. Chen, M. Matsuo, Y. Nagata, G. Ritter, E. Jager, H. Nomura, S. Kondo, I. Tawara, T. Kato, H. Shiku, L. J. Old, J. E. Galán, S. Gnjatic, In vivo antigen delivery by a Salmonella typhimurium type III secretion system for therapeutic cancer vaccines. J. Clin. Invest. 116, 1946-1954 (2006).
22. C. Grillot-Courvalin, S. Goussard, F. Huetz, D. M. Ojcius, P. Courvalin, Functional gene transfer from intracellular bacteria to mammalian cells. Nat. Biotechnol. 16, 862-866 (1998).
23. M. Loeffler, G. Le'Negrate, M. Krajewska, J. C. Reed, Attenuated Salmonella engineered to produce human cytokine LIGHT inhibit tumor growth. Proc. Natl. Acad. Sci. U.S.A. 104, 12879-12883 (2007).
24. M. Loeffler, G. Le'Negrate, M. Krajewska, J. C. Reed, Salmonella typhimurium engineered to produce CCL21 inhibit tumor growth. Cancer Immunol. Immunother. 58, 769-775 (2009).
25. S. E. Lee, S. Y. Kim, B. C. Jeong, Y. R. Kim, S. J. Bae, O. S. Ahn, J.-J. Lee, H.-C. Song, J. M. Kim, H. E. Choy, S. S. Chung, M.-N. Kweon, J. H. Rhee, A bacterial flagellin, Vibrio vulnificus FlaB, has a strong mucosal adjuvant activity to induce protective immunity. Infect. Immun. 74, 694-702 (2006).
26. C. T. Nguyen, S. H. Hong, J.-I. Sin, H. V. D. Vu, K. Jeong, K. O. Cho, S. Uematsu, S. Akira, S. E. Lee, J. H. Rhee, Flagellin enhances tumor-specific CD8+ T cell immune responses through TLR5 stimulation in a therapeutic cancer vaccine model. Vaccine 31, 3879-3887 (2013).
27. J.-E. Kim, T. X. Phan, V. H. Nguyen, H.-V. Dinh-Vu, J. H. Zheng, M. Yun, S.-G. Park, Y. Hong, H. E. Choy, M. Szardenings, W. Hwang, J.-A. Park, S. Park, S.-H. Im, J.-J. Min, Salmonella typhimurium suppresses tumor growth via the pro-inflammatory cytokine interleukin-1b. Theranostics 5, 1328-1342 (2015).
28. T. X. Phan, V. H. Nguyen, M. T.-Q. Duong, Y. Hong, H. E. Choy, J.-J. Min, Activation of inflammasome by attenuated Salmonella typhimurium in bacteria-mediated cancer therapy. Microbiol. Immunol. 59, 664-675 (2015).
29. U. N. Le, H.-S. Kim, J.-S. Kwon, M. Y. Kim, V. H. Nguyen, S. N. Jiang, B.-I. Lee, Y. Hong, M. G. Shin, J. H. Rhee, H.-S. Bom, Y. Ahn, S. S. Gambhir, H. E. Choy, J.-J. Min, Engineering and visualization of bacteria for targeting infarcted myocardium. Mol. Ther. 19, 951-959 (2011).
30. S.-P. Lei, H.-C. Lin, S.-S. Wang, J. Callaway, G. Wilcox, Characterization of the Erwinia carotovora pelB gene and its product pectate lyase. J. Bacteriol. 169, 4379-4383 (1987).
31. Z. Y. Cai, A. Sanchez, Z. C. Shi, T. T. Zhang, M. Y. Liu, D. K. Zhang, Activation of Toll-like receptor 5 on breast cancer cells by flagellin suppresses cell proliferation and tumor growth. Cancer Res. 71, 2466-2475 (2011).
32. X. Xiao, I. Gaffar, P. Guo, J. Wiersch, S. Fischbach, L. Peirish, Z. Song, Y. El-Gohary, K. Prasadan, C. Shiota, G. K. Gittes, M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7. Proc. Natl. Acad. Sci. U.S.A. 111, E1211-E1220 (2014).
33. K. A. Kigerl, J. C. Gensel, D. P. Ankeny, J. K. Alexander, D. J. Donnelly, P. G. Popovich, Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J. Neurosci. 29, 13435-13444 (2009).
34. C.-H. Lee, C.-L. Wu, A.-L. Shiau, Toll-like receptor 4 mediates an antitumor host response induced by Salmonella choleraesuis. Clin. Cancer Res. 14, 1905-1912 (2008).
35. C.-H. Lee, C.-L. Wu, A.-L. Shiau, Salmonella choleraesuis as an anticancer agent in a syngeneic model of orthotopic hepatocellular carcinoma. Int J Cancer 122, 930-935 (2008).
36. E. Di Carlo, G. Forni, P. Lollini, M. P. Colombo, A. Modesti, P. Musiani, The intriguing role of polymorphonuclear neutrophils in antitumor reactions. Blood 97, 339-345 (2001).
37. H. Kanzler, F. J. Barrat, E. M. Hessel, R. L. Coffman, Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat. Med. 13, 552-559 (2007).
38. L. Wang, Q. Liu, Q. Sun, C. Zhang, T. Chen, X. Cao, TLR4 signaling in cancer cells promotes chemoattraction of immature dendritic cells via autocrine CCL20. Biochem. Biophys. Res. Commun. 366, 852-856 (2008).
39. S. Tsuji, M. Matsumoto, O. Takeuchi, S. Akira, I. Azuma, A. Hayashi, K. Toyoshima, T. Seya, Maturation of human dendritic cells by cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guérin: Involvement of Toll-like receptors. Infect. Immun. 68, 6883-6890 (2000).
40. K. De Filippo, R. B. Henderson, M. Laschinger, N. Hogg, Neutrophil chemokines KC and macrophage-inflammatory protein-2 are newly synthesized by tissue macrophages using distinct TLR signaling pathways. J. Immunol. 180, 4308-4315 (2008).
41. S. Rakoff-Nahoum, R. Medzhitov, Toll-like receptors and cancer. Nat. Rev. Cancer 9, 57-63 (2009).
42. N. Wang, H. Liang, K. Zen, Molecular mechanisms that influence the macrophage M1-M2 polarization balance. Front. Immunol. 5, 614 (2014).
43. S. K. Biswas, L. Gangi, S. Paul, T. Schioppa, A. Saccani, M. Sironi, B. Bottazzi, A. Doni, B. Vincenzo, F. Pasqualini, L. Vago, M. Nebuloni, A. Mantovani, A. Sica, A distinct and unique transcriptional program expressed by tumor-Associated macrophages (defective NF-kB and enhanced IRF-3/STAT1 activation). Blood 107, 2112-2122 (2006).
44. L. Sfondrini, A. Rossini, D. Besusso, A. Merlo, E. Tagliabue, S. Mènard, A. Balsari, Antitumor activity of the TLR-5 ligand flagellin in mouse models of cancer. J. Immunol. 176, 6624-6630 (2006).
45. J.-M. Reichh art, TLR5 takes aim at bacterial propeller. Nat. Immunol. 4, 1159-1160 (2003).
46. M. Y. Song, H. J. Kim, E. Y. Kim, M. S. Shin, H. C. Lee, Y. J. Hong, J. H. Rhee, H. Yoon, S. Ryu, S. Lim, H. E. Choy, ppGpp-dependent stationary phase induction of genes on Salmonella pathogenicity island 1. J. Biol. Chem. 279, 34183-34190 (2004).
47. S. Uematsu, M. H. Jang, N. Chevrier, Z. Guo, Y. Kumagai, M. Yamamoto, H. Kato, N. Sougawa, H. Matsui, H. Kuwata, H. Hemmi, C. Coban, T. Kawai, K. J. Ishii, O. Takeuchi, M. Miyasaka, K. Takeda, S. Akira, Detection of pathogenic intestinal bacteria by Toll-like receptor 5 on intestinal CD11c+ lamina propria cells. Nat. Immunol. 7, 868-874 (2006).
48. O. Adachi, T. Kawai, K. Takeda, M. Matsumoto, H. Tsutsui, M. Sakagami, K. Nakanishi, S. Akira, Targeted disruption of the MyD88 gene results in loss of il-1-And il-18-mediated function. Immunity 9, 143-150 (1998).
49. A. Rajput, I. Dominguez San Martin, R. Rose, A. Beko, C. LeVea, E. Sharratt, R. Mazurchuk, R. M. Hoffman, M. G. Brattain, J. Wang, Characterization of HCT116 human colon cancer cells in an orthotopic model. J. Surg. Res. 147, 276-281 (2008).
50. X. Zhang, R. Goncalves, D. M. Mosser, The isolation and characterization of murine macrophages. Curr. Protoc. Immunol10.1002/0471142735.im1401s83 (2008).
51. T. Saito, H. Nishikawa, H. Wada, Y. Nagano, D. Sugiyama, K. Atarashi, Y. Maeda, M. Hamaguchi, N. Ohkura, E. Sato, H. Nagase, J. Nishimura, H. Yamamoto, S. Takiguchi, T. Tanoue, W. Suda, H. Morita, M. Hattori, K. Honda, M. Mori, Y. Doki, S. Sakaguchi, Two FOXP3+CD4+ T cell subpopulations distinctly control the prognosis of colorectal cancers. Nat. Med. 22, 679-684 (2016).
52. O. A. Ali, D. Emerich, G. Dranoff, D. J. Mooney, In situ regulation of DC subsets and T cells mediates tumor regression in mice. Sci. Transl. Med. 1, 8ra19 (2009).