Antigen Presenting Cells (APCs)
399
approach to obtain endogenous antigen
synthesis in DCs has been to fuse DCs to
tumor cells. The immunogenicity of such
vaccines was conFrmed in several experi-
mental systems, although the mechanisms
leading to the clinical success of allogeneic
approaches remained open.
The alternative strategy foresees to pro-
vide tumor antigens exogenously. To this
end, tumor cell lysates and deFned tu-
mor antigens, applied as a protein or a
peptide, were coincubated with autologous
DCs so that MHC class II–restricted pep-
tide antigens become cross-presented. An
alternative to this latter strategy is to pre-
pare exosomes from the respective tumor
cells. Exosomes are the internal vesicles
of multivesicular endosomes. They were
shown to contain tumor rejection antigens
andtobeab
letot
ran
s
fe
rthemtoDC
s
,
so that tumor-speciFc CTL responses are
generated in mice. Although several clin-
ical trials – where DC-based vaccination
was employed in the context of malig-
nant melanoma, lymphoma, myeloma,
prostate, and renal cancer – were success-
ful to a certain extent, there are still
several potential caveats that have to be
taken into account. Some tumor anti-
gens are not tumor-speciFc but tissue-
speciFc and hence widely expressed in
normal tissues. In case of vaccination
with melanocyte/melanoma antigens, this
leads to vitiligo due to autoimmunity at
the vaccination site. Conversely, the im-
munoproteasome of DCs may process
tumor antigens in a way that is different
from processing by the normal proteasome
being active in tumor cells. Moreover, feed-
ing DCs with whole tumor cell lysates
is risky since T cells that are not di-
rected against tumor antigens may be
primed as well. Therefore, precise knowl-
edge of MHC class I–and MHC class
II–associated tumor-speciFc peptide anti-
gens is necessary. Unfortunately, only a
few class II–restricted helper epitopes are
known so far. Therefore, further effort is
needed to obtain a more comprehensive
set of tumor-speciFc peptide epitopes in
order to optimize DC-based vaccination
against major malignancies.
See also
Dendritic Cells.
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