Tumor-associated antigens - Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - page 153

stimulating factor (GM-CSF), which is used as an adjuvant to enhance the
immune response, were shown to elicit anti-tumor responses [76] . Most
clinical trials with GVAX have enrolled patients with solid malignancies
[77] . However, GVAX was also shown to be effective in pre-clinical stud-
ies with hematological malignancies. In a mouse model, Borrello et al.
showed that immunization with irradiated GM-CSF-transduced B-cell
lymphoma tumor cells in the early post-transplant period decreased
the incidence of tumor relapse [78] . In a phase II trial in patients with
AML, a mixed GVAX platform (autologous leukemia cells and GM-CSF-
secreting K562 cells) was given to patients along with autologous stem
cell transplantation and adoptive immunotherapy of vaccine-primed
lymphocytes. In this study, cellular and humoral immune responses
were detected in patients following the vaccine. Additionally, a reduc-
tion in minimal residual disease was observed in some patients [79] .
Current trials are ongoing to further study the therapeutic role of GVAX
in myeloid leukemia.

APC-based vaccines

Another way to augment immunity against TAA without limiting the
immune response to a predetermined epitope is by using APC, specifically
DC, as part of the targeted approach ( Figure 7.2 ). Since the tumor micro-
environment, to include leukemia, was shown to promote functional and
quantitative immune defects [80] , enhancing antigen presentation by APCs
in patients with leukemia by either exposing the APCs to an antigen ex vivo
or by modifying their endogenous antigen repertoire has shown promising
results.

155

In one approach using DC vaccines, mRNA for known TAA is introduced
into the DC, which is then naturally processed and presented after expres-
sion by the DC. Although this methodology allows for the presentation
of the most dominant epitopes from the TAA and is not HLA-restricted,

FIGURE 7.2
Eliciting immunity using antigen presenting cells
(APCs). In order to elicit immune responses against
TAAs without prior knowledge of the presented epitope
or HLA-restriction, APC can be pulsed with leukemia
cells, TAAs or can be transfected with virus or plasmid
containing the sequence for the TAA. Once the TAA
is intracellular, either following cross-presentation or
expression by the APC, it can undergo antigen pro-
cessing and presentation on MHC class I and II. This
will in turn elicit CD8 + and CD4 + immune responses.