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Background
Lymphodepletion, reconstitution and active-specific tumour cell vaccination (LRAST)
enhances the tumour-specific immune response in a murine melanoma model. Myeloid derived
suppressor cells (MDSC, Gr-1+ CD11b+) may decrease the induction of T-cells and their
therapeutic efficacy. Aim of the study was to evaluate the benefit of MDSC depletion
in addition to LRAST, using anti-Gr-1 antibody (Ab). The Gr-1 epitope is also expressed
on CD8+ T-cells.
Methods
Female C57BL/6 mice with subcutaneous (s.c.) D5 melanoma were lymphodepleted with
cyclophosphamide and reconstituted with naïve splenocytes. Vaccination was performed
with irradiated syngeneic mGM-CSF-producing D5G6 melanoma cells. For MDSC depletion,
anti-Gr-1 Ab (clone RB6-8C5, 230 μg) was injected every other day starting on the day of lymphodepletion. Induction
of tumour-specific T-cells in tumour vaccine draining lymph nodes was evaluated using
interferon (IFN)-γ assays. Immune cells were analysed by flow cytometry. D5 tumour growth was monitored.
Results
Anti-Gr-1 administration had no long-lasting effect on MDSC elimination. The antibody
also bound to CD8+ Gr-1+ CD44+ T memory cells. The combination of anti-Gr-1 treatment
and LRAST enhanced tumour-specific IFN-γ release. Nevertheless, this did not translate into improved survival.
Conclusions
Given an insufficient elimination of MDSC and the possible depletion of Gr-1+ memory
T-cells, the use of anti-Gr-1 Ab in our tumour model seems questionable.
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