Plastics, Analysis

Elgert, K. F.

doi:10.1002/14356007.a20_509

Cited by 1 publication

(1 citation statement)

References 32 publications

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“…14 TAM recruitment, activation, growth and differentiation are regulated by macrophage colony-stimulating factor (M-CSF, also known as colony-stimulating factor 1, CSF-1). [15][16] High pretreatment serum M-CSF is a strong independent predictor of poor survival in PC patients. 17 In PC mouse models, blockade of M-CSF or its receptor not only suppresses tumor angiogenesis and lymphangiogenesis 18 but also improves response to T-cell checkpoint immunotherapies that target programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4).…”

Section: Introductionmentioning

confidence: 99%

Novel TREM-1 Inhibitors Attenuate Tumor Growth and Prolong Survival in Experimental Pancreatic Cancer

Sigalov

2017

Mol. Pharmaceutics

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Pancreatic cancer (PC) is a highly lethal cancer with an urgent need to expand the limited treatment options for patients. Tumor-associated macrophages (TAMs) promote tumor aggressiveness and metastasis. High expression of triggering receptor expressed on myeloid cells 1 (TREM-1) on TAMs directly correlates with poor survival in patients with non-small cell lung cancer (NSCLC). We have previously hypothesized that blockade of TREM-1 could be a promising therapeutic strategy to treat cancer and shown that the novel, ligand-independent TREM-1 inhibitory peptides rationally designed using the signaling chain homooligomerization (SCHOOL) strategy suppress NSCLC growth in vivo. Here, we evaluated the therapeutic potential of these inhibitors in three human PC xenograft mouse models. Administration of SCHOOL peptides resulted in a strong antitumor effect achieving an optimal treatment/control (T/C) value of 19% depending on the xenograft and formulation used and persisting even after treatment was halted. The effect correlated significantly with increased survival and suppressed TAM infiltration. The peptides were well-tolerated when deployed either in free form or formulated into lipopeptide complexes for peptide half-life extension and targeted delivery. Finally, blockade of TREM-1 significantly reduced serum levels of interleukin (IL)-1α, IL-6, and macrophage colony-stimulating factor (M-CSF), but not vascular endothelial growth factor, suggesting M-CSF-dependent antitumor mechanisms. Collectively, these promising data suggest that SCHOOL TREM-1-specific peptide inhibitors have a cancer type independent, therapeutically beneficial antitumor activity and can be potentially used as a stand-alone therapy or as a component of combinational therapy for PC, NSCLC, and other solid tumors.

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Section: Introductionmentioning

confidence: 99%