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- Title
M860, a Monoclonal Antibody against Human Lactoferrin, Enhances Tumoricidal Activity of Low Dosage Lactoferrin via Granzyme B Induction.
- Authors
Li, Ya; Li, Jie; Gong, Zheng; Pan, Xiao-Hua; Ma, Zi-Han; Ma, Shu-Yan; Wang, Hong-Min; Dong, Hong-Liang; Gong, Fang-Yuan; Gao, Xiao-Ming
- Abstract
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.
- Subjects
LACTOFERRIN; GRANZYMES; MONOCLONAL antibodies; IMMUNE complexes; DRUG dosage; MONOCYTES; CELL lines
- Publication
Molecules, 2019, Vol 24, Issue 20, p3640
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules24203640