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Navidea Biopharmaceuticals, Inc.
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Study:Blocking SIRPα/CD47 reduces lung cancer growth-edifies NAVB TAM preclin results(Navidea) reducing tumor growth by 76% via M1/M2 reprogramming This 2022 study out of China in mice edify Navidea's preclinical results on the blockade of SIRPα/CD47 reprogramming M1/M2 ratio, and in this study reduced lung cancer cells in WT mice and abolished in KO mice.
Lack of SIRP-alpha reduces lung cancer growth in mice by promoting anti-tumour ability of macrophages and neutrophils 1Department of Pulmonary Medicine,Zhongshan Hospital, Fudan University,Shanghai, China2Department of Thoracic Surgery, HuadongHospital, Fudan University, Shanghai, China3Shanghai Key Laboratory of LungInflammation and Injury, Shanghai, ChinaCorrespondenceZhilong Jiang and Lijuan Hu, Department ofPulmonary Medicine, Zhongshan Hospital,Fudan University Shanghai, 180 Fenglin Road,Shanghai, 200032, China.Email:jiang.zhilong@zs- Abstract Objectives: Signal regulatory protein-alpha (SIRPα) is a transmembrane glycoproteinspecifically expressed on myeloid cells. Blockade of SIRPα/CD47 interaction is effective in combinational therapy of some cancers. This study aimed to explore into the role and underlying molecular mechanisms of SIRPα in lung cancer growth. Materials and Methods: A mouse model with lung cancer in wild-type (WT) and SIRPα-knockout mouse (KO) mice was established by subcutaneous injection of Lewis murine lung cancer cells (LLC). Circulating monocytes and neutrophils were depleted in mice by intraperitoneal administration of clodronate liposomes and anti-Ly6G antibody, respectively. Phenotypes and phagocytosis of macrophages and neutrophils were analysed by flow cytometry. Transwell assay was used to analyse LLC cells migration and invasion. Results: Lack of SIRPα inhibited LLC cells growth in KO mice, associated with reduced infiltrating PD-1+CD8+T cells and production of IL-6 from infiltrating macrophages and neutrophils in tumour tissues. Depletion of circulating monocytes and neutrophils reduced LLC cells growth in WT mice, which was abolished in KO mice. Studies in vitro showed that lack of SIRPα increased M1/M2 ratio, and reduced LLC cell migration and invasion via attenuated IL-6 secretion. Lack of SIRPα expression in neutrophils effectively increased the cytotoxic activity to LLC cells in vitro. Conclusions: Lack of SIRPα suppressed lung cancer cell growth in mice, dependent on circulating macrophages and neutrophils, in association with improved phagocytosis and reduced IL-6 expression |
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