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

Abstract

Lymphodepletion, 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) 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. Female 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. MDSC depletion was performed using anti-Gr-1 Ab (clone RB6-8C5). 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. LRAST 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. Additional anti-Gr-1 mAb administration in LRAST-treated mice delayed growth of D5 melanomas by two weeks. Furthermore, we elucidate the impact of anti-Gr-1-depleting antibodies on the memory T cell compartment. Our 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.

Deciphering the mechanism of Peptostreptococcus anaerobius-induced chemoresistance in colorectal cancer: the important roles of MDSC recruitment and EMT activation

“…Anti-Gr-1 mAb can selectively cut down MDSCs ( 34 ) and has no obvious influence on other immune cells, then anti-Gr-1 mAb (200 μg/mouse, three times/week) was intraperitoneally injected in mice to eliminate MDSCs both in the bone marrow ( Figure 3B ) and in the tumor microenvironment ( Figures 3C, D ). It was interesting to find out that the tumor was evidently diminished while MDSCs were eliminated by Anti-Gr-1 in the PA +OXA+Anti-Gr-1 group compared with the PA +OXA group ( Figure 2E ), and tumor was also diminished in the Anti-Gr-1-control group compared with the M group; however, there was no statistically significant difference.…”

Programable Albumin-Hitchhiking Nanobodies Enhance the Delivery of STING Agonists to Potentiate Cancer Immunotherapy

“…S18). We also used anti-Gr1 antibodies to deplete MDSCs (primarily gMDSCs) 51 and again found a modest reduction in nAlb-diABZI e cacy (Fig. S19).…”

Combining all-trans retinoid acid treatment targeting myeloid-derived suppressive cells with cryo-thermal therapy enhances antitumor immunity in breast cancer

“…A number of studies in mouse tumor models have reported that MDSC depletion promotes T cell-dependent antitumor responses ( 27 , 28 ). In our previous studies, we found that the release of HSP70 induced by cryo-thermal therapy promoted the differentiation of MDSCs into DCs and macrophages ( 13 ).…”