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

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.

COVID-19 in Recent Lung Transplant Recipients: Clinical Outcomes and Management Strategies.

BACKGROUND: COVID-19 causes a wide range of symptoms, with particularly high risk of severe respiratory failure and death in patients with predisposing risk factors such as advanced age or obesity. Recipients of solid organ transplants, and in particular lung transplantation, are more susceptible to viral infection owing to immune suppressive medication. As little is known about the SARS-CoV-2 infection in these patients, this study was undertaken to describe outcomes and potential management strategies in early COVID-19 infection early after lung transplantation. METHODS: We describe the incidence and outcome of COVID-19 in a cohort of recent lung transplant recipients in Munich. Six of 186 patients who underwent lung transplantation in the period between March 2019 and March 2021 developed COVID-19 within the first year after transplantation. We documented the clinical course and laboratory changes for all patients showing differences in the severity of the infection with COVID-19 and their outcomes. RESULTS: Three of 6 SARS-CoV-2 infections were hospital-acquired and the patients were still in inpatient treatment after lung transplantation. All patients suffered from symptoms. One patient did not receive antiviral therapy. Remdesivir was prescribed in 4 patients and the remaining patient received remdesivir, bamlanivimab and convalescent plasma. CONCLUSIONS: COVID-19 does not appear to cause milder disease in lung transplant recipients compared with the general population. Immunosuppression is potentially responsible for the delayed formation of antibodies and their premature loss. Several comorbidities and a general poor preoperative condition showed an extended hospital stay.