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172 Bot and Obrocea
Figure 13 Cancer vaccine design as guided by the immune nature of target antigens.
and the overall success of the program during drug development, and
further, in the marketplace. It is particularly important, for cancer vaccines
in development, to consider this point and take into account the diversity of
prospective mechanisms of action, since there is still much debate on the
significance of preexisting immunity or tolerance relative to the potential
efficiency of vaccination (Fig. 13).
l Implement a biomarker-guided eligibility-criteria approach to maximize
the opportunity of the investigational drug during the exploratory phase. In
this case, exclude patients that do not express within the tumor tissue the
target antigens or do not display a given HLA type and therefore will not
have any reasonable chance for clinically benefiting, should the pharmacological
response be present.
The overarching message is to optimize the approach through exploration before
advancing to randomized efficacy trials (phase 2b) and certainly, confirmatory
pivotal trials used for registration. These conclusions were further used in concordance
with a translational approach (bedside to bench) in order to optimize
the investigational drug prior to further development (Fig. 2).
From a mechanistic point of view, the emerging view based on preclinical
and clinical studies is that irrespective of how many APCs are exposed to the