Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

Fig. 10.6 Multiple different strategies lead to
successful vaccination in tumor models by convergence
into a common mechanistic pathway.
A wide variety of different approaches have
proved effective in animal models of tumor rejection
[40], including transfer of genes encoding
multiple cytokines [41, 42], co-stimulatory molecules
[43, 44], foreign immunogens [45], allogeneic
MHC molecules [46, 47], cytotoxic genes
[48], heat shock proteins [49], etc. Vaccinations
have been achieved with defined tumor antigens
[4, 5], antigen-loaded DCs [12, 50±53] and auto-
10.7 Combining the Best of Both Worlds
logous/allogeneic cell vaccines [88, 90]. In addition,
there is a much older history of the use of
adjuvants based on various bacterial and other
materials [54±56]. It is, however, now possible to
rationalize the apparently highly diverse range of
successful approaches into a few common principles.
A synthesis of the literature indicates that
most successful immunotherapies for cancer
culminate in a common pathway which starts by
tumor cell killing leading to antigen release, uptake
by APCs and presentation in a fully activated
environment.
most of the above steps can be bypassed by simply loading activated DCs with tumor
antigen ex vivo and using adoptive transfer of these cells to the patient, although caution
must always be retained in case the antitumor therapy becomes so successful in
breaking tolerance to tumor antigens that it is accompanied by the induction of autoimmunity
to the related normal tissues [76]. Clinical trials using DCs loaded with tumor
antigens have already shown considerable promise, confirming that these cells,
their antigenic load and their state of activation lie firmly on the key pathways to effective
tumor vaccination (see, e.g. [50, 77]).
The outstanding significance of tumor cell killing is that it leads to antigen release
and the mechanism of cell killing is important because it needs to lead to antigen re-
219