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

tel-00827710, version 1 - 29 May 2013
be loaded with tumor peptides or genetically modified to express the whole tumor antigen;
and (iii) these cells can be expanded to large numbers ex vivo allowing for the injection of
sufficient cell-associated antigen into patients. For instance, Russo and colleagues injected T
cells modified to express the tyrosinase-related protein 2 (TRP-2), a TAA specific for
melanoma, into B16F10 tumor-bearing mice and observed a protective immunity (Russo et
al., 2007). They convincingly demonstrated that CD8α + DCs phagocytosed genetically
modified T cells, matured and cross-presented antigen. Thus the response observed was not
due to direct presentation of antigen by T cells. This promising mouse study was followed by
an initial clinical trial (Fontana et al., 2009).
B. Stimulation of the immune response by adjuvants
Adjuvants are compounds that are injected in parallel with antigens to “help” the immune
response by increasing the immunonogenicity of the antigen through a variety of mechanisms.
Initially, the effects of adjuvants were discovered empirically: they were used to enhance the
adaptive immune response and the effectiveness was evaluated by the antibody titers
generated and level of protection that was conferred. Traditionally, adjuvants were used to
boost the immune response against a specific antigen and, therefore, allowed for the use of
lower antigen doses to confer protection. In recent years, another aspect of adjuvant function
has been thoroughly explored and developed: the ability of adjuvant to modulate the quality
and outcome of the T cell response. The combination of adjuvants and antigen, in some cases,
will result in the generation of immunity that would not be induced by the antigen alone
(Coffman et al., 2010). For instance, using a specific adjuvant injection strategy, it is possible
to manipulate the balance between the Th1 versus Th2 response, or CD4 versus CD8
responsiveness; moreover, particular adjuvants can be selected to induce the generation of
memory cells or decrease the time required for the development of an adaptive immune
response. Although the first adjuvants were identified empirically, today there is a growing
body of work that further characterizes the signaling pathways implicated in adjuvant activity.
This increased understanding will allow for more targeted and specific modulation of the
immune response during vaccination, as well as identify and support the development of the
next generation of adjuvants.
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