Cancer stem cell based adjuvant for oncoantingen-driven vaccination

The aim of this work is the identification of adjuvant molecules that can be associated to an oncoantigen-driven vaccination. By microarray analysis and data mining we have identified a set of drugs targeting genes that are associated to breast cancer stem cells (CSC): Atorvastatin, Bumetanide, Radafaxine, ICA 17043. YSL. In vitro characterization of one of these drugs, Atorvastatin. showed its ability to impair mammosphere formation, which is a peculiarity of normal and cancer stem cells. A mathematical model to simulate the effect of the combination of adjuvant and vaccination was designed and parameters defined on the basis of ErbB2-driven vaccination and Atorvastatin activity on CSC. The model suggests that reduction and halting of tumor mass increment can be reached by combining the effect of ErbB2 vaccination and 5 μM Atorvastatin as adjuvant.

[1]  R. Weinberg,et al.  Cancer stem cells: mirage or reality? , 2009, Nature Medicine.

[2]  Dr. Andreas von Deimling Neoplasia , 1997, Laboratory investigation; a journal of technical methods and pathology.

[3]  Piero Musiani,et al.  DNA Vaccination Against Rat Her-2/Neu p185 More Effectively Inhibits Carcinogenesis Than Transplantable Carcinomas in Transgenic BALB/c Mice1 2 , 2000, The Journal of Immunology.

[4]  G. Forni,et al.  Oncoantigens as anti-tumor vaccination targets: the chance of a lucky strike? , 2008, Cancer Immunology, Immunotherapy.

[5]  Federica Cavallo,et al.  Sca-1 identifies the tumor-initiating cells in mammary tumors of BALB-neuT transgenic mice. , 2008, Neoplasia.

[6]  M. Kohandel,et al.  Investigating the link between epithelial-mesenchymal transition and the cancer stem cell phenotype: A mathematical approach. , 2010, Journal of theoretical biology.

[7]  Raffaele A Calogero,et al.  Regulation of leukemic cell differentiation and retinoid-induced gene expression by statins , 2009, Molecular Cancer Therapeutics.

[8]  Federica Cavallo,et al.  Vaccines for tumour prevention , 2006, Nature Reviews Cancer.

[9]  Ling Xia,et al.  Cancer stem cell, niche and EGFR decide tumor development and treatment response: A bio-computational simulation study. , 2011, Journal of theoretical biology.

[10]  M. Frank,et al.  The therapeutic promise of the cancer stem cell concept. , 2010, The Journal of clinical investigation.

[11]  Eibert R. Heerdink,et al.  A Comparison of Two Multiple-Characteristic Decision-Making Models for the Comparison of Antihypertensive Drug Classes , 2006, American journal of cardiovascular drugs : drugs, devices, and other interventions.

[12]  T. Jacks,et al.  Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer , 2005, Cell.

[13]  M. Clarke,et al.  Stem Cells and Cancer: Two Faces of Eve , 2006, Cell.

[14]  Federica Cavallo,et al.  2011: the immune hallmarks of cancer , 2011, Cancer Immunology, Immunotherapy.

[15]  Federica Cavallo,et al.  Are oncoantigens suitable targets for anti-tumour therapy? , 2007, Nature Reviews Cancer.