Work

Anti-Gr-1 Antibody Provides Short-Term Depletion of MDSC in Lymphodepleted Mice with Active-Specific Melanoma Therapy

Year: 2022

Type: article

Abstract: BackgroundLymphodepletion, reconstitution and active-speciﬁc tumor cell vaccination (LRAST) enhances the induction of tumor-speciﬁc T cells in a murine melanoma model. Myeloid-derived suppressor cells (MDSC, Gr-1+ CD11b+) may counteract the induction of tumor-reactive T cells and their therapeutic eﬃcacy. Thus, the aim of the study was to evaluate a possible beneﬁt of MDSC depletion using anti-Gr-1 antibodies (Ab) in combination with LRAST.MethodsFemale C57BL/6 mice with 3 days established subcutaneous (s.c.) D5 melanoma were lymphodepleted with cyclophosphamide and reconstituted with naive splenocytes. Vaccination was performed with irradiated syngeneic mGM-CSF-secreting 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 tumor-speciﬁc T cells derived from tumor vaccine draining lymph nodes (TVDLN) was evaluated by the amount of tumor-specific interferon (IFN)- γ release. Tumor growth was monitored following active-specific vaccination with or without anti-Gr-1 Ab administration.ResultsLRAST combined with anti-Gr-1 mAb administration enhanced the induction of tumor-specific T cells in TVDLN capable of releasing IFN-γ in a tumor-specific manner. In mice treated with LRAST and anti-Gr-1 mAb growth of D5 melanoma cells was significantly delayed for two weeks following tumor injection as compared to mice with LRAST treatment alone. Furthermore, we elucidate the impact of anti-Gr-1 depleting antibodies on the memory T cell compartment.ConclusionOur data indicate that standard of care treatment regimens against cancer can be improved by implementing agents, e.g. depleting antibodies, which target and eliminate MDSC.

Source: Vaccines

DOI: 10.3390/vaccines10040560

Authors: Peter Rose, Natasja K. van den Engel, Julia R. Kovacs, Rudolf A. Hatz, Louis Boon, Hauke Winter