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tel-00827710, version 1 - 29 May 2013<br />

Figure 57. Combination and sequence of administration of different approaches for cancer<br />

therapy. From the known actions of the different therapeutic agents, we propose a mo<strong>de</strong>l to choose<br />

the optimal timing of <strong>de</strong>livery. Arrows and lines represent the optimal time window for each treatment<br />

<strong>de</strong>pending on the step it is supposed to act.<br />

Although, we chose to <strong>de</strong>scribe how to apply our data and mo<strong>de</strong>l to the <strong>de</strong>velopment of anti-<br />

cancer therapy, the same strategies may be applied to other diseases where different<br />

approaches and combinations might be required to optimize current patient treatment.<br />

IV. CONCLUSION<br />

In conclusion, we have used a mo<strong>de</strong>l of cell-associated antigen to perform a thorough, careful<br />

anaysis of the CD8 + T cell response after cross-presentation. The <strong>de</strong>velopment of the<br />

t<strong>et</strong>ramer-based enrichment strategy and its combination with other approaches such as<br />

intracellular cytokine staining or immunoscope allowed us to perform an in-<strong>de</strong>pth study of the<br />

kin<strong>et</strong>ics, phenotype and functionality of the endogenous CD8 + T cell response.<br />

We applied these strategies to study first the impact of the route of immunization on CD8 + T<br />

cell cross-priming. We compared the efficiency and effectiveness of local versus systemic<br />

176

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