Modeling and simulation of cancer immunoprevention vaccine

Pappalardo, Francesco; Lollini, Pier‐Luigi; Castiglione, Filippo; Motta, Santo

doi:10.1093/bioinformatics/bti426

Cited by 98 publications

(72 citation statements)

References 16 publications

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“…SIMTRIPLEX has been used to model immunoprevention vaccines Pappalardo et al 2005Pappalardo et al , 2006Lollini et al 2006) and atherosclerosis (Pappalardo et al 2008a). Rather than describe the work covered in the preceding papers, here we will consider the modelling and computational challenges that we have faced.…”

Section: Modelling the Immune Systemmentioning

confidence: 99%

ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale

Halling‐Brown

Pappalardo

Rapin

et al. 2010

Phil. Trans. R. Soc. A.

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The ultimate aim of the EU-funded ImmunoGrid project is to develop a natural-scale model of the human immune system-that is, one that reflects both the diversity and the relative proportions of the molecules and cells that comprise it-together with the * Author for correspondence (a.shepherd@mail.cryst.bbk.ac.uk). † The authors of this paper belong to the ImmunoGrid Consortium. grid infrastructure necessary to apply this model to specific applications in the field of immunology. These objectives present the ImmunoGrid Consortium with formidable challenges in terms of complexity of the immune system, our partial understanding about how the immune system works, the lack of reliable data and the scale of computational resources required.In this paper, we explain the key challenges and the approaches adopted to overcome them. We also consider wider implications for the present ambitious plans to develop natural-scale, integrated models of the human body that can make contributions to personalized health care, such as the European Virtual Physiological Human initiative.Finally, we ask a key question: How long will it take us to resolve these challenges and when can we expect to have fully functional models that will deliver health-care benefits in the form of personalized care solutions and improved disease prevention?

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Section: Modelling the Immune Systemmentioning

confidence: 99%

ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale

Halling‐Brown

Pappalardo

Rapin

et al. 2010

Phil. Trans. R. Soc. A.

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“…However, this differential efficacy of the cancer vaccine in prophylaxis and therapy has been proven by several other studies evaluating the feasibility of a cancer vaccine with tolerized tumor antigens. [42][43][44][45][46] Novakovic et al 44 found that the proportion of protected mice was 75-100% by vaccination of irradiated melanoma tumor cells with CpG ODN in a prophylactic setting whereas the rates of cured mice were only 11.1-21.1% in a therapeutic setting. Garcia-Hernandez Mde et al 45 recently reported that prophylactic vaccination with a prostate antigen, six-transmembrane epithelial antigen of prostate, significantly delayed tumor growth and improved survival whereas therapeutic vaccination induced a modest delay in the growth of established prostate tumors.…”

Section: Differential Antitumor Effects Of Il-23 H-t Jin Et Almentioning

confidence: 99%

“…Moreover, in a HER-2/neu transgenic mouse model which closely mimics the natural history of human tumors, early vaccination produced a significantly delay in the onset of tumors, whereas late vaccination was completely devoid of an effect in comparison to untreated control mice. 42,46 There are many reasons why vaccination is poorly effective as a tumor therapy. 1 One of them is the lag time of inducing tumor-specific adaptive immunity, leading to the generation of an immunosuppressive environment by the growing tumor in a therapeutic setting.…”

Section: Differential Antitumor Effects Of Il-23 H-t Jin Et Almentioning

confidence: 99%

Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

Youn

et al. 2008

Cancer Gene Ther

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A novel cytokine interleukin (IL)-23 bears a structural and functional resemblance to IL-12. A recombinant adenovirus expressing IL-23N220L (recombinant replication-defective adenovirus (rAd)/IL-23N220L) that selectively secrets IL-23 was constructed and compared with rAd/IL-12N220L in terms of immunological and antitumor effects. In a prophylactic setting, vaccination with rAd/ ovalbumin (OVA) and rAd/IL-23N220L enhanced OVA-specific CD8 þ T-cell responses that were closely associated with complete protection against the subsequent challenge of OVA-expressing E.G7 thymoma. However, in a therapeutic setting, the intratumoral injection of rAd/IL-23N220L showed only marginal antitumor activity against several established tumors such as E.G7, CT26 and B16F10. Interestingly, whereas IL-23 still induced tumor-specific CD8 þ T-cell responses, it could not activate natural killer (NK) cells in vitro and in vivo. In addition, the adoptive transfer of activated NK cells partially restored the therapeutic antitumor effect of IL-23, indicating that NK cells are one of the crucial factors responsible for the regression of established tumors. Taken together, we demonstrated that adenovirus-mediated gene transfer of IL-23 induces a potent prophylactic, but not a therapeutic, antitumor effect.

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“…In so doing, they assembled a number of up-to-date immunological theories in one single coherent and generalpurpose model that has shown to be a valid starting point to explore different medical/clinical subjects. In the past years we have developed specialized versions of the Celada-Seiden model to study HIV-1 infection, EBV infection, hypersensitivity reactions and cancer immunoprevention (described respectively in [12][13][14][15] Figure 1. The aim of the presented simulation platform is to provide enough complexity to be able to implement virtually any process in immunology.…”

Section: Introductionmentioning

confidence: 99%

A Modeling Framework For Immune-related Diseases

Castiglione

Motta

Pappalardo

et al. 2012

Math. Model. Nat. Phenom.

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Abstract. About twenty five years ago the first discrete mathematical model of the immune system was proposed. It was very simple and stylized. Later, many other computational models have been proposed each one adding a certain level of sophistication and detail to the description of the system. One of these, the Celada-Seiden model published back in 1992, was already mature at its birth, setting apart from the topic-specific nature of the other models. This one was not just a model but rather a framework with which one could implement his own immunological theories.Here we describe this computational framework, developed to perform simulations of different pathologies that are directly or indirectly connected to the immune system. We briefly describe the system first, then we report on few applications so to give the reader a clear idea of its practical utility in clinical research problems.

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Modeling and simulation of cancer immunoprevention vaccine

Abstract: http://www.dmi.unict.it/CIG/suppdata_bioinf.html.

Cited by 98 publications

References 16 publications

ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale

ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale

Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

A Modeling Framework For Immune-related Diseases

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