Systems biology applied to vaccine and immunotherapy development

Molecular Biology and Viral Oncology, Dept of Experimental Oncology, Istituto Nazionale Tumori Fond Pascale, Via Mariano Semmola 142, 80131 Napoli, Italy.
BMC Systems Biology (Impact Factor: 2.44). 09/2011; 5(1):146. DOI: 10.1186/1752-0509-5-146
Source: PubMed


Immunotherapies, including vaccines, represent a potent tool to prevent or contain disease with high morbidity or mortality such as infections and cancer. However, despite their widespread use, we still have a limited understanding of the mechanisms underlying the induction of protective immune responses.
Immunity is made of a multifaceted set of integrated responses involving a dynamic interaction of thousands of molecules; among those is a growing appreciation for the role the innate immunity (i.e. pathogen recognition receptors - PRRs) plays in determining the nature and duration (immune memory) of adaptive T and B cell immunity. The complex network of interactions between immune manipulation of the host (immunotherapy) on one side and innate and adaptive responses on the other might be fully understood only employing the global level of investigation provided by systems biology.
In this framework, the advancement of high-throughput technologies, together with the extensive identification of new genes, proteins and other biomolecules in the "omics" era, facilitate large-scale biological measurements. Moreover, recent development of new computational tools enables the comprehensive and quantitative analysis of the interactions between all of the components of immunity over time.
Here, we review recent progress in using systems biology to study and evaluate immunotherapy and vaccine strategies for infectious and neoplastic diseases. Multi-parametric data provide novel and often unsuspected mechanistic insights while enabling the identification of common immune signatures relevant to human investigation such as the prediction of immune responsiveness that could lead to the improvement of the design of future immunotherapy trials. Thus, the paradigm switch from "empirical" to "knowledge-based" conduct of medicine and immunotherapy in particular, leading to patient-tailored treatment.

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Available from: Maria Lina Tornesello
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    • "In fact, a significant proportion of the human cancer vaccine trials to date are targeted against embryonic antigens such as carcinoembryonic antigen (Greiner et al., 2002) cancer/testes antigen (Chiriva- Internati, 2011; Mirandola et al., 2011) and α-fetoprotein etc (Toyoda et al., 2011). Unfortunately, targeting one antigen alone is unlikely to generate effective antitumor immune responses to mediate tumor rejection because of rapid appearance of escape mutants and the general inefficiency of monovalent cancer vaccines (Buonaguro et al., 2011; Durrant et al., 2011). Interestingly, it was found that cancer stem cells (CSCs) and embryonic stem cells (ESCs) shared similar cell surface markers and antigens not presented by adult tissues, which played a part in metastasis, angiogenesis and increased chemoradiotherapy resistance in cancer (Field et al., 2010; Kee et al., 2012; Lopez et al., 2012), so immune response against ESCs RESEARCH ARTICLE "
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