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M860, a Monoclonal Antibody against Human Lactoferrin, Enhances Tumoricidal Activity of Low Dosage Lactoferrin via Granzyme B Induction

1
The Institute of Biology and Medical Sciences, Soochow University, Suzhou 215123, China
2
Key Laboratory of Systemic Biomedicine of Suzhou, Suzhou 215000, China
*
Authors to whom correspondence should be addressed.
Molecules 2019, 24(20), 3640; https://doi.org/10.3390/molecules24203640
Received: 9 August 2019 / Revised: 1 October 2019 / Accepted: 2 October 2019 / Published: 9 October 2019
Lactoferrin (LF) is a soluble glycoprotein of the transferring family found in most biological fluids, functioning as a major first line defense molecule against infection in mammals. It also shows certain anti-tumor activity, but its clinical application in tumor therapy is limited because high dosage is required. In this study, we demonstrate that M860, a monoclonal antibody against human LF (hLF), could significantly increase the anti-tumor potential of low dosage hLF by forming LF-containing immune complex (IC). Human monocytes primed with LF-IC, but not hLF or M860 alone, or control ICs, showed strong tumoricidal activity on leukemia cell lines Jurkat and Raji through induction of secreted Granzyme B (GzB). LF-IC is able to colligate membrane-bound CD14 (a TLR4 co-receptor) and FcγRIIa (a low affinity activating Fcγ receptor) on the surface of human monocytes, thereby triggering the Syk-PI3K-AKT-mTOR pathway leading to GzB production. Our work identifies a novel pathway for LF-mediated tumoricidal activity and may extend the clinical application of LF in tumor therapy. View Full-Text
Keywords: Lactoferrin Immune-Complex; Granzyme B; Monocytes; tumoricidal activity Lactoferrin Immune-Complex; Granzyme B; Monocytes; tumoricidal activity
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Li, Y.; Li, J.; Gong, Z.; Pan, X.-H.; Ma, Z.-H.; Ma, S.-Y.; Wang, H.-M.; Dong, H.-L.; Gong, F.-Y.; Gao, X.-M. M860, a Monoclonal Antibody against Human Lactoferrin, Enhances Tumoricidal Activity of Low Dosage Lactoferrin via Granzyme B Induction. Molecules 2019, 24, 3640.

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