Combining anaerobic bacterial oncolysis with vaccination that blocks interleukin-10 signaling may achieve better outcomes for late stage cancer management

Figures & data

Table 1. Combing both Anaerobic bacteria oncolysis and therapeutic vaccination may achieve better outcome for late stage cancer management.

Ref	Year	Strategy/Result
^104	1947	Intravenous injection of C.histolyticium spores resulted in tumor lysis
^68	1957	Immunosurvilliance theroy formly formulated
^76	2003	Immunization and IL10 signaling blockade enhances vaccine induced CD8 T cell responses
^105	2005	Recombinant C. acetobutylicum for IL2 resulted in enhanced anti-tumor effect
^65	2008	Anarobic bacteria treatment leads to chemokine secretion and recruit Tcells to tumor site
^71	2010	First therapeutic vaccine against prostate cancer approved by FDA
^58	2012	Clostridium novyi NT spores elicits therapeutic effects in dog naturally occurring tumors
^46	2014	Immunization and IL10 signaling blockade prevent tumor growth in a mouse transplant tumor model
^59	2014	Administration of C. novyi NT to a patient with advanced leiomyosarcoma was effective at inducing tumor regression

Table 2. Bacterial oncolysis result in local tumor inflammation responses.

Bacteriolytic therapy	Inflammatory responses in tumor	Systemic inflammatory responses	Year	References
Clostridium novyi-NT	Neutrophil, Monocytes and Lymphocytes infiltration	Increased IL6, MIP-2, G-CSF, TIMP-1 CD8+ T cells are tumor killing effector cells	2004	^20
Salmonella	Expression of IFNγ, IP-10; CD4, CD8 T cells infiltration Increased cell death		2008	^65
Salmonella	Increased expression of IFNγ, MIG, IP-10	Increased IFNγ Bacteriolytic effect is TLR4 dependent	2008	^64
Salmonella	Neutrophil, Macrophage infiltration	T cell deficient mice have lower tumor inhibition rate compared with wild-type mice	2011	^66

Parker RC, Plummer HC, Siebenmann CO, Chapman MG. Effect of histolyticus infection and toxin on transplantable mouse tumors. Proc Soc Exp Biol Med 1947; 66:461-467; PMID:18921791; http://dx.doi.org/10.3181/00379727-66-16124

 PubMed Web of Science ®Google Scholar

Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3:991-998; PMID:12407406; http://dx.doi.org/10.1038/ni1102-991

 PubMed Web of Science ®Google Scholar

Liu XS, Xu Y, Hardy L, Khammanivong V, Zhao W, Fernando GJ, Leggatt GR, Frazer IH. IL-10 mediates suppression of the CD8 T cell IFN-gamma response to a novel viral epitope in a primed host. J Immunol 2003; 171:4765-4772; PMID:14568953; http://dx.doi.org/10.4049/jimmunol.171.9.4765

 PubMed Web of Science ®Google Scholar

Barbe S, Van Mellaert L, Theys J, Geukens N, Lammertyn E, Lambin P, Anne J. Secretory production of biologically active rat interleukin-2 by Clostridium acetobutylicum DSM792 as a tool for anti-tumor treatment. FEMS Microbiol Lett 2005; 246:67-73; PMID:15869963; http://dx.doi.org/10.1016/j.femsle.2005.03.037

 PubMed Web of Science ®Google Scholar

Lee CH, Wu CL, Shiau AL. Salmonella choleraesuis as an anticancer agent in a syngeneic model of orthotopic hepatocellular carcinoma. Int J Cancer 2008; 122:930-935; PMID:17960612; http://dx.doi.org/10.1002/ijc.23047

 PubMed Web of Science ®Google Scholar

Jacobs JJ, Snackey C, Geldof AA, Characiejus D, Van Moorselaar RJ, Den Otter W. Inefficacy of therapeutic cancer vaccines and proposed improvements Casus of prostate cancer. Anticancer Res 2014; 34:2689-2700; PMID:24922629

 PubMed Web of Science ®Google Scholar

Krick EL, Sorenmo KU, Rankin SC, Cheong I, Kobrin B, Thornton K, Kinzler KW, Vogelstein B, Zhou S, Diaz LA, Jr. Evaluation of Clostridium novyi-NT spores in dogs with naturally occurring tumors. Am J Vet Res 2012; 73:112-118; PMID:22204296; http://dx.doi.org/10.2460/ajvr.73.1.112

 PubMed Web of Science ®Google Scholar

Chen S, Wang X, Wu X, Wei MQ, Zhang B, Liu X, Wang Y. IL-10 signalling blockade at the time of immunization inhibits Human papillomavirus 16 E7 transformed TC-1 tumour cells growth in mice. Cell Immunol 2014; 290:145-151; PMID:24983823; http://dx.doi.org/10.1016/j.cellimm.2014.06.002

 PubMed Web of Science ®Google Scholar

Roberts NJ, Zhang L, Janku F, Collins A, Bai RY, Staedtke V, Rusk AW, Tung D, Miller M, Roix J, et al. Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses. Science Translational Medicine 2014; 6:249ra111; PMID:25122639; http://dx.doi.org/10.1126/scitranslmed.3008982

 PubMed Web of Science ®Google Scholar

Agrawal N, Bettegowda C, Cheong I, Geschwind JF, Drake CG, Hipkiss EL, Tatsumi M, Dang LH, Diaz LA, Jr, Pomper M, et al, Bacteriolytic therapy can generate a potent immune response against experimental tumors. Proc Natl Acad Sci U S A 2004; 101:15172-15177; PMID:15471990; http://dx.doi.org/10.1073/pnas.0406242101

 PubMed Web of Science ®Google Scholar

Lee CH, Hsieh JL, Wu CL, Hsu PY, Shiau AL. T cell augments the antitumor activity of tumor-targeting Salmonella. Appl Microbiol Biotechnol 2011; 90:1381-1388; PMID:21360146; http://dx.doi.org/10.1007/s00253-011-3180-z

 PubMed Web of Science ®Google Scholar