肿瘤细菌疗法综述
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摘要
早在150年前,活细菌就已经被用来治疗癌症。1868年,德国医生Busch首先报道了部分肿瘤患者在感染肺炎链球菌后,体内的肿瘤生长被抑制甚至被彻底清除。在之后的三十年内,美国医生Coley和另外一名德国医生Fehleisen又分别报道了细菌感染可以抑制肿瘤这一现象。由于其结果难以重复,细菌的毒力也难以控制,这些早期的研究工作一直存在争议。然而经过严谨的动物实验,细菌的侵染被证实确实可以使肿瘤变小,宿主的免疫系统也会在治疗的过程中被激活。文章将尝试综述肿瘤细菌疗法的发展历程和展望其发展方向。
As early as in the second half of the 19 th century, bacteria have already been used to treat cancer patients. In 1868, German doctor W. Busch reported that when patients with Sarcoma were intentionally infected by Streptococcus pyrogenes, the tumors were suppressed or eliminated. Later, similar cases of bacterial cancer treatments were reported by American doctor William B. Coley and German doctor Friedrich Fehleisen, independently. However, these early attempts remain controversial due to lack of repeatability and safety. In recent years, systematically designed animal experiments have proved that bacterial treatments can effectively suppress tumor growth and also stimulate immune system of the hosts. In this article, we will try to give out an outline of the history, development and future of bacterial cancer therapy.
As early as in the second half of the 19 th century, bacteria have already been used to treat cancer patients. In 1868, German doctor W. Busch reported that when patients with Sarcoma were intentionally infected by Streptococcus pyrogenes, the tumors were suppressed or eliminated. Later, similar cases of bacterial cancer treatments were reported by American doctor William B. Coley and German doctor Friedrich Fehleisen, independently. However, these early attempts remain controversial due to lack of repeatability and safety. In recent years, systematically designed animal experiments have proved that bacterial treatments can effectively suppress tumor growth and also stimulate immune system of the hosts. In this article, we will try to give out an outline of the history, development and future of bacterial cancer therapy.
引文
[1]Pawelek JM,Low KB,Bermudes D.Bacteria as tumour-targeting vectors[J].The Lancet Oncology,2003,4(9):548-556.
[2]Fehleisen F.Die etiologie des erysipels[M].Berlin:Theodor Fischer,1883:48.
[3]Coley WB.II.Contribution to the knowledge of sarcoma[J].Annals of Surgery,1891,14(6):199-220.
[4]Nauts HC,Swift WE,Coley BL.The treatment of malignant tumors by bacterial toxins as developed by the late William B.Coley,M.D.,reviewed in the light of modern research[J].Cancer Research,1946,6:205-216.
[5]Nauts HC,Fowler GA,Bogatko FH.A review of the infl uence of bacterial infection and of bacterial products(Coley’s toxins)on malignant tumors in man;a critical analysis of 30 inoperable cases treated by Coley’s mixed toxins,in which diagnosis was confi rmed by microscopic examination selected for special study[J].Acta Medica Scandinavica,Supplementum,1953,276:1-103.
[6]Coley WB.The treatment of inoperable sarcoma by bacterial toxins(the mixed toxins of the Streptococcus erysipelas and the Bacillus prodigiosus)[J].Proceedings of Royal Society Medicine,1910,3(Surg Sect):1-48.
[7]Balkwill F.Tumour necrosis factor and cancer[J].Nature Reviews Cancer,2009,9(5):361-371.
[8]Alexandroff AB,Jackson AM,O'Donnell MA,et al.BCG immunotherapy of bladder cancer:20 years on[J].Lancet,1999,353(9165):1689-1694.
[9]Van Mellaert L,BarbéS,AnnéJ.Clostridium spores as anti-tumour agents[J].Trends in Microbiology,2006,14(4):190-196.
[10]Malmgren RA,Flanigan CC.Localization of the vegetative form of Clostridium tetani in mouse tumors following intravenous spore administration[J].Cancer Research,1955,15(7):473-478.
[11]Mse JR,Mse G.Oncolysis by clostridia.I.Activity of Clostridium butyricum(M-55)and other nonpathogenic clostridia against the Ehrlich carcinoma[J].Cancer Research,1964,24:212-216.
[12]Dang LH,Bettegowda C,Huso DL,et al.Combination bacteriolytic therapy for the treatment of experimental tumors[J].Proceedings of the National Academy of Sciences of the United States of America,2001,98(26):15155-15160.
[13]Roberts NJ,Zhang LP,Janku F,et al.Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses[J].Science Translational Medicine,2014,6(248):249ra111.
[14]Goldin BR,Gorbach SL.Effect of Lactobacillus a-dimethylhydrazine dihydrochloride-induced intestinal cancer in rats[J].Journal of the National Cancer Institute,1980,64(2):263-265.
[15]Kimura NT,Taniguchi S,Aoki K,et al.Selective lifidum in mouse tumors following intravenous administration[J].Cancer Research,1980,40(6):2061-2068.
[16]Biff i A,Cntiproliferative effect of fermented milk on the growth of a human breast cancer cell line[J].Nutrition and Cancer,1997,28(1):93-99.
[17]Murosaki S,Muroyama K,Yamamoto Y,et al.Antitumor effect of heat-killed Lactobacillusplantarum L-137 through restoration of impaired interleukin-12 production in tumor-bearing mice[J].Cancer Immunology,Immunotherapy,2000,49(3):157-164.
[18]Yazawa K,Fujimori M,Amano J,et al.Bifidobacterium longum as a delivery system for cancer gene therapy:selective localization and growth in hypoxic tumors[J].Cancer Gene Therapy,2000,7(2):269-274.
[19]Carswell EA,Old LJ,Kassel RL,et al.An endotoxin-induced serum factor that causes necrosis of tumors[J].Proceedings of the National Academy of Sciences of the United States of America,1975,72(9):3666-3670.
[20]Beg AA,Baltimore D.An essential role for NFkappa B in preventing TNF-alpha-induced cell death[J].Science,1996,274(5288):782-784.
[21]Karbach J,Neumann A,Brand K,et al.Phase I clinical trial of mixed bacterial vaccine(Coley’s toxins)in patients with NY-ESO-1 expressing cancers:immunological effects and clinical activity[J].Clinical Cancer Research,2012,18(19):5449-5459.
[22]Luo Y,Han R,Evanoff DP,et al.Interleukin-10inhibits Mycobacterium bovis bacillus CalmetteGuerin(BCG)-induced macrophage cytotoxicity against bladder cancer cells[J].Clinical and Experimental Immunology,2010,160(3):359-368.
[23]Yuksel ZS,Buber E,Kocagoz T,et al.Mycobacterial strains that stimulate the immune system most efficiently as candidates for the treatment of bladder cancer[J].Journal of Molecular Microbiology and Biotechnology,2011,20(1):24-28.
[24]Newton MR,Askeland EJ,Andresen ED,et al.Anti-interleukin-10R1 monoclonal antibody in combination with bacillus Calmette--Guerin is protective against bladder cancer metastasis in a murine orthotopic tumour model and demonstrates systemic specific anti-tumour immunity[J].Clinical and Experimental Immunology,2014,177(1):261-268.
[25]Pawelek JM,Low KB,Bermudes D.Tumortargeted Salmonella as a novel anticancer vector[J].Cancer Research,1997,57(20):4537-4544.
[26]Bermudes D,Low B,Pawelek J.Tumor-targeted Salmonella.Highly selective delivery vectors[J].Advances in Experimental Medicine and Biology,2000,465:57-63.
[27]Toso JF,Gill VJ,Hwu P,et al.Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma[J].Journal of Clinical Oncology,2002,20(1):142-152.
[28]Yu B,Yang M,Shi L,et al.Explicit hypoxia targeting with tumor suppression by creating an"obligate"anaerobic Salmonella typhimurium strain[J].Scientifi c Reports,2012,2:436.
[29]Akin D,Sturgis J,Ragheb K,et al.Bacteria-mediated delivery of nanoparticles and cargo into cells[J].Nature Nanotechnology,2007,2:441-449.
[30]Quispe-Tintaya W,Chandra D,Jahangir A,et al.Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(21):8668-8673.
[31]Theys J,Landuyt W,Nuyts S,et al.Specific targeting of cytosine deaminase to solid tumors by engineered Clostridium acetobutylicum[J].Cancer Gene Therapy,2001,8(4):294-297.
[32]Xiang S,Fruehauf J,Li CJ.Short hairpin RNAexpressing bacteria elicit RNA interference in mammals[J].Nature Biotechnology,2006,24(6):697-702.
[33]Danino T,Prindle A,Kwong GA,et al.Programmable probiotics for detection of cancer in urine[J].Science Translational Medicine,2015,7(289):289ra84.
[2]Fehleisen F.Die etiologie des erysipels[M].Berlin:Theodor Fischer,1883:48.
[3]Coley WB.II.Contribution to the knowledge of sarcoma[J].Annals of Surgery,1891,14(6):199-220.
[4]Nauts HC,Swift WE,Coley BL.The treatment of malignant tumors by bacterial toxins as developed by the late William B.Coley,M.D.,reviewed in the light of modern research[J].Cancer Research,1946,6:205-216.
[5]Nauts HC,Fowler GA,Bogatko FH.A review of the infl uence of bacterial infection and of bacterial products(Coley’s toxins)on malignant tumors in man;a critical analysis of 30 inoperable cases treated by Coley’s mixed toxins,in which diagnosis was confi rmed by microscopic examination selected for special study[J].Acta Medica Scandinavica,Supplementum,1953,276:1-103.
[6]Coley WB.The treatment of inoperable sarcoma by bacterial toxins(the mixed toxins of the Streptococcus erysipelas and the Bacillus prodigiosus)[J].Proceedings of Royal Society Medicine,1910,3(Surg Sect):1-48.
[7]Balkwill F.Tumour necrosis factor and cancer[J].Nature Reviews Cancer,2009,9(5):361-371.
[8]Alexandroff AB,Jackson AM,O'Donnell MA,et al.BCG immunotherapy of bladder cancer:20 years on[J].Lancet,1999,353(9165):1689-1694.
[9]Van Mellaert L,BarbéS,AnnéJ.Clostridium spores as anti-tumour agents[J].Trends in Microbiology,2006,14(4):190-196.
[10]Malmgren RA,Flanigan CC.Localization of the vegetative form of Clostridium tetani in mouse tumors following intravenous spore administration[J].Cancer Research,1955,15(7):473-478.
[11]Mse JR,Mse G.Oncolysis by clostridia.I.Activity of Clostridium butyricum(M-55)and other nonpathogenic clostridia against the Ehrlich carcinoma[J].Cancer Research,1964,24:212-216.
[12]Dang LH,Bettegowda C,Huso DL,et al.Combination bacteriolytic therapy for the treatment of experimental tumors[J].Proceedings of the National Academy of Sciences of the United States of America,2001,98(26):15155-15160.
[13]Roberts NJ,Zhang LP,Janku F,et al.Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses[J].Science Translational Medicine,2014,6(248):249ra111.
[14]Goldin BR,Gorbach SL.Effect of Lactobacillus a-dimethylhydrazine dihydrochloride-induced intestinal cancer in rats[J].Journal of the National Cancer Institute,1980,64(2):263-265.
[15]Kimura NT,Taniguchi S,Aoki K,et al.Selective lifidum in mouse tumors following intravenous administration[J].Cancer Research,1980,40(6):2061-2068.
[16]Biff i A,Cntiproliferative effect of fermented milk on the growth of a human breast cancer cell line[J].Nutrition and Cancer,1997,28(1):93-99.
[17]Murosaki S,Muroyama K,Yamamoto Y,et al.Antitumor effect of heat-killed Lactobacillusplantarum L-137 through restoration of impaired interleukin-12 production in tumor-bearing mice[J].Cancer Immunology,Immunotherapy,2000,49(3):157-164.
[18]Yazawa K,Fujimori M,Amano J,et al.Bifidobacterium longum as a delivery system for cancer gene therapy:selective localization and growth in hypoxic tumors[J].Cancer Gene Therapy,2000,7(2):269-274.
[19]Carswell EA,Old LJ,Kassel RL,et al.An endotoxin-induced serum factor that causes necrosis of tumors[J].Proceedings of the National Academy of Sciences of the United States of America,1975,72(9):3666-3670.
[20]Beg AA,Baltimore D.An essential role for NFkappa B in preventing TNF-alpha-induced cell death[J].Science,1996,274(5288):782-784.
[21]Karbach J,Neumann A,Brand K,et al.Phase I clinical trial of mixed bacterial vaccine(Coley’s toxins)in patients with NY-ESO-1 expressing cancers:immunological effects and clinical activity[J].Clinical Cancer Research,2012,18(19):5449-5459.
[22]Luo Y,Han R,Evanoff DP,et al.Interleukin-10inhibits Mycobacterium bovis bacillus CalmetteGuerin(BCG)-induced macrophage cytotoxicity against bladder cancer cells[J].Clinical and Experimental Immunology,2010,160(3):359-368.
[23]Yuksel ZS,Buber E,Kocagoz T,et al.Mycobacterial strains that stimulate the immune system most efficiently as candidates for the treatment of bladder cancer[J].Journal of Molecular Microbiology and Biotechnology,2011,20(1):24-28.
[24]Newton MR,Askeland EJ,Andresen ED,et al.Anti-interleukin-10R1 monoclonal antibody in combination with bacillus Calmette--Guerin is protective against bladder cancer metastasis in a murine orthotopic tumour model and demonstrates systemic specific anti-tumour immunity[J].Clinical and Experimental Immunology,2014,177(1):261-268.
[25]Pawelek JM,Low KB,Bermudes D.Tumortargeted Salmonella as a novel anticancer vector[J].Cancer Research,1997,57(20):4537-4544.
[26]Bermudes D,Low B,Pawelek J.Tumor-targeted Salmonella.Highly selective delivery vectors[J].Advances in Experimental Medicine and Biology,2000,465:57-63.
[27]Toso JF,Gill VJ,Hwu P,et al.Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma[J].Journal of Clinical Oncology,2002,20(1):142-152.
[28]Yu B,Yang M,Shi L,et al.Explicit hypoxia targeting with tumor suppression by creating an"obligate"anaerobic Salmonella typhimurium strain[J].Scientifi c Reports,2012,2:436.
[29]Akin D,Sturgis J,Ragheb K,et al.Bacteria-mediated delivery of nanoparticles and cargo into cells[J].Nature Nanotechnology,2007,2:441-449.
[30]Quispe-Tintaya W,Chandra D,Jahangir A,et al.Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(21):8668-8673.
[31]Theys J,Landuyt W,Nuyts S,et al.Specific targeting of cytosine deaminase to solid tumors by engineered Clostridium acetobutylicum[J].Cancer Gene Therapy,2001,8(4):294-297.
[32]Xiang S,Fruehauf J,Li CJ.Short hairpin RNAexpressing bacteria elicit RNA interference in mammals[J].Nature Biotechnology,2006,24(6):697-702.
[33]Danino T,Prindle A,Kwong GA,et al.Programmable probiotics for detection of cancer in urine[J].Science Translational Medicine,2015,7(289):289ra84.