Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s Toxin
Several decades after Coley’s initial work, we here systematically analyzed tumoricidal as well as immunostimulatory effects of the historical preparation Coley’s Toxin (CT), a safe vaccine made of heat-inactivated S. pyogenes and S. marcescens. First, by performing in vitro analysis, established hu...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2012/230625 |
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| author | C. Maletzki U. Klier W. Obst B. Kreikemeyer M. Linnebacher |
| author_facet | C. Maletzki U. Klier W. Obst B. Kreikemeyer M. Linnebacher |
| author_sort | C. Maletzki |
| collection | DOAJ |
| description | Several decades after Coley’s initial work, we here systematically analyzed tumoricidal as well as immunostimulatory effects of the historical preparation Coley’s Toxin (CT), a safe vaccine made of heat-inactivated S. pyogenes and S. marcescens. First, by performing in vitro analysis, established human pancreatic carcinoma cell lines responded with dose- and time-dependent growth inhibition. Effects were attributed to necrotic as well as apoptotic cell death as determined by increased Caspase 3/7 levels, raised numbers of cells with sub-G1-DNA, and induced p expression, indicative for cell cycle arrest. Besides, CT effectively stimulated human peripheral blood leukocytes (huPBL) from healthy volunteers. Quantitative gene expression analysis revealed upregulated mRNA levels of selected Toll-like receptors. Flow cytometric phenotyping of CT-stimulated huPBLs identified raised numbers of CD25+-activated leukocytes. In vivo, repetitive, local CT application was well tolerated by animals and induced considerable delay of Panc02 tumors. However, systemic treatment failed to affect tumor growth. Antitumoral effects following local therapy were primarily accompanied by stimulation of innate immune mechanisms. Data presented herein prove that the historical approach of using killed bacteria as active immunotherapeutic agents still holds promise, and further careful preclinical analyses may pave the way back into clinical applications. |
| format | Article |
| id | doaj-art-e24d9452a2734ede890fc17f20919932 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-e24d9452a2734ede890fc17f209199322025-02-03T01:11:19ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/230625230625Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s ToxinC. Maletzki0U. Klier1W. Obst2B. Kreikemeyer3M. Linnebacher4Section of Molecular Oncology and Immunotherapy, Department of General, Vascular, Thoracic and Transplantation Surgery, Schillingallee 69, 18055 Rostock, GermanySection of Molecular Oncology and Immunotherapy, Department of General, Vascular, Thoracic and Transplantation Surgery, Schillingallee 69, 18055 Rostock, GermanyDivision of Gastroenterology, Department of Internal Medicine, University of Rostock, 18055 Rostock, GermanyDepartment of Medical Microbiology and Hospital Hygiene, Institute of Medical Microbiology, Virology and Hygiene, University of Rostock, 18055 Rostock, GermanySection of Molecular Oncology and Immunotherapy, Department of General, Vascular, Thoracic and Transplantation Surgery, Schillingallee 69, 18055 Rostock, GermanySeveral decades after Coley’s initial work, we here systematically analyzed tumoricidal as well as immunostimulatory effects of the historical preparation Coley’s Toxin (CT), a safe vaccine made of heat-inactivated S. pyogenes and S. marcescens. First, by performing in vitro analysis, established human pancreatic carcinoma cell lines responded with dose- and time-dependent growth inhibition. Effects were attributed to necrotic as well as apoptotic cell death as determined by increased Caspase 3/7 levels, raised numbers of cells with sub-G1-DNA, and induced p expression, indicative for cell cycle arrest. Besides, CT effectively stimulated human peripheral blood leukocytes (huPBL) from healthy volunteers. Quantitative gene expression analysis revealed upregulated mRNA levels of selected Toll-like receptors. Flow cytometric phenotyping of CT-stimulated huPBLs identified raised numbers of CD25+-activated leukocytes. In vivo, repetitive, local CT application was well tolerated by animals and induced considerable delay of Panc02 tumors. However, systemic treatment failed to affect tumor growth. Antitumoral effects following local therapy were primarily accompanied by stimulation of innate immune mechanisms. Data presented herein prove that the historical approach of using killed bacteria as active immunotherapeutic agents still holds promise, and further careful preclinical analyses may pave the way back into clinical applications.http://dx.doi.org/10.1155/2012/230625 |
| spellingShingle | C. Maletzki U. Klier W. Obst B. Kreikemeyer M. Linnebacher Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s Toxin Clinical and Developmental Immunology |
| title | Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s Toxin |
| title_full | Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s Toxin |
| title_fullStr | Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s Toxin |
| title_full_unstemmed | Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s Toxin |
| title_short | Reevaluating the Concept of Treating Experimental Tumors with a Mixed Bacterial Vaccine: Coley’s Toxin |
| title_sort | reevaluating the concept of treating experimental tumors with a mixed bacterial vaccine coley s toxin |
| url | http://dx.doi.org/10.1155/2012/230625 |
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