Voie d'immunisation et séquence d'administration de l ... - TEL

tel-00827710, version 1 - 29 May 2013
Figure 1. Successful vaccines and challenging infectious diseases. Pathogens are classified
depending on the requirement of T cell-immunity and/or humoral response for their clearance, as well
as on their antigen stability. TB, Tuberculosis. Figure from Rappuoli et al., 2011.
In contrast to the many successful vaccines developed against infectious diseases, few
vaccines exist that provide protection against cancer. The concept of cancer immunotherapy
first appeared at the end of the 19 th century, when Coley observed a tumor reduction upon the
injection of bacterial products into the tumor and applied this strategy to the treatment of
inoperable sarcomas. Many studies have been performed to further understand the interactions
between tumor cells, their microenvironment and, in particular, immune cells. The
identification of tumor-associated antigens, the discovery of dendritic cells (DCs), as well as
the central role of cytotoxic CD8 + T cells in tumor clearance had raised expectations for the
development and successful use of tumor vaccines in the clinic. Unfortunately, several
mechanisms of tumor-mediated immunosuppression have also been identified, making this
goal increasingly complex. Additionaly, cancer vaccines need to be therapeutic, rather than
prophylactic, which creates additional complexity when trying to elicit an immune response
while also combating tumor-associated immune regulation. Numerous approaches have thus
far failed to provide reproducible clinical efficiency despite the development of a measurable
anti-tumor response in patients in some cases (Lesterhuis et al., 2011).
For the treatment of cancer, as well as for chronic diseases or infectious agents such as HIV or
plasmodium, efficient vaccines eliciting robust T cell responses are urgently needed. This is
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