Home
/
Data resources
/
Literature
/
21870996
Lethal iron deprivation induced by non-neutralizing antibodies targeting transferrin receptor 1 in malignant B cells.

Leuk Lymphoma, 2011/11;52(11):2169-78.

Rodríguez JA[1], Luria-Pérez R, López-Valdés HE, Casero D, Daniels TR, Patel S, Avila D, Leuchter R, So S, Ortiz-Sánchez E, Bonavida B, Martínez-Maza O, Charles AC, Pellegrini M, Helguera G, Penichet ML

Affiliations

PMID: 21870996DOI: 10.3109/10428194.2011.596964

Impact factor: 2.996

Abstract
A number of antibodies have been developed that induce lethal iron deprivation (LID) by targeting the transferrin receptor 1 (TfR1/CD71) and either neutralizing transferrin (Tf) binding, blocking internalization of the receptor and/or inducing its degradation. We have developed recombinant antibodies targeting human TfR1 (ch128.1 and ch128.1Av), which induce receptor degradation and are cytotoxic to certain malignant B-cells. We now show that internalization of TfR1 bound to these antibodies can lead to its sequestration and degradation, as well as reduced Tf uptake, and the induction of a transcriptional response consistent with iron deprivation, which is mediated in part by downstream targets of p53. Cells resistant to these antibodies do not sequester and degrade TfR1 after internalization of the antibody/receptor complex, and accordingly maintain their ability to internalize Tf. These findings are expected to facilitate the rational design and clinical use of therapeutic agents targeting iron import via TfR1 in hematopoietic malignancies.
MeSH terms
Animals; Antibodies; Antigens, CD; B-Lymphocytes; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Deferoxamine; Endocytosis; Gene Expression Profiling; Humans; Immunoblotting; Iron; Mice; Mice, SCID; Multiple Myeloma; Oligonucleotide Array Sequence Analysis; Protein Binding; Receptors, Transferrin; Reverse Transcriptase Polymerase Chain Reaction; Siderophores; Transferrin; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays
More resources
EndNote: Download