The role of talactoferrin alfa in the treatment of non-small cell lung cancer

Kelly, Ronan J.; Giaccone, Giuseppe

doi:10.1517/14712598.2010.512914

Cited by 15 publications

(9 citation statements)

References 31 publications

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“…These findings have limited both the systemic use and therapeutic potential of first generation ACPs, and presently the only major candidate in this class of peptides with promise for medical use is the neutraceutical protein, lactoferrin (Table ), which has been patented as an anticancer agent . In previous human clinical trials, orally administered lactoferrin was shown to reduce the risk of colon carcinogenesis, and currently the protein is in an advanced human clinical trials as an orally administered treatment for nonsmall lung cell cancer (Table ) . The strategy adopted by most efforts to design a therapeutically useful second generation ACPs seems to be primarily focused on optimizing the structural and physiochemical parameters of these peptides for this use .…”

Section: Discussionmentioning

confidence: 99%

“…316 In previous human clinical trials, orally administered lactoferrin was shown to reduce the risk of colon carcinogenesis, 317 and currently the protein is in an advanced human clinical trials as an orally administered treatment for nonsmall lung cell cancer (Table III). [318][319][320] The strategy adopted by most efforts to design a therapeutically useful second generation ACPs seems to be primarily focused on optimizing the structural and physiochemical parameters of these peptides for this use. [321][322][323] Based on the findings of this review, we suggest that the most efficient strategies for the design of therapeutically useful ACPs will be those which take into account the characteristics of not only these peptides, but also those of their target cancer cell membranes.…”

Section: Discussionmentioning

confidence: 99%

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On the selectivity and efficacy of defense peptides with respect to cancer cells

Harris

Dennison

Singh³

et al. 2011

Medicinal Research Reviews

162

148

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Here, we review potential determinants of the anticancer efficacy of innate immune peptides (ACPs) for cancer cells. These determinants include membrane-based factors, such as receptors, phosphatidylserine, sialic acid residues, and sulfated glycans, and peptide-based factors, such as residue composition, sequence length, net charge, hydrophobic arc size, hydrophobicity, and amphiphilicity. Each of these factors may contribute to the anticancer action of ACPs, but no single factor(s) makes an overriding contribution to their overall selectivity and toxicity. Differences between the anticancer actions of ACPs seem to relate to different levels of interplay between these peptide and membrane-based factors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

On the selectivity and efficacy of defense peptides with respect to cancer cells

Harris

Dennison

Singh³

et al. 2011

Medicinal Research Reviews

162

148

View full text Add to dashboard Cite

show abstract

“…Through the induction of IFN‐γ secretion and the activation of CD8 + T and NKT cells, oral TLF inhibits ERBB2‐driven mammary carcinogenesis in transgenic mice and the growth of transplantable tumors (15). TLF has also been (16–18) and is currently being investigated (19) as a therapeutic anticancer agent in clinical trials.…”

mentioning

confidence: 99%

Recombinant human lactoferrin induces human and mouse dendritic cell maturationviaToll‐like receptors 2 and 4

Spadaro¹,

Arigoni²,

Cantarella³

et al. 2013

FASEB j.

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Lactoferrin, a key component of innate immunity, is a cationic monomeric 80-kDa glycoprotein of the transferrin superfamily. Recombinant human lactoferrin, known as talactoferrin (TLF), induces a distinct functional maturation program in human dendritic cells (DCs) derived from peripheral blood monocytes. However, the receptors and molecular mechanisms involved in this induction have not been fully determined. By exploiting genome-wide transcription profiling of immature DCs, TNF-α- and IL-1β-matured DCs (m-DCs), and TLF-matured DCs (TLF-DCs), we have detected a set of transcripts specific for m-DCs and one specific for TLF-DCs. Functional network reconstruction highlighted, as expected, the association of m-DC maturation with IL-1β, TNF-α, and NF-κB, whereas TLF-DC maturation was associated with ERK and NF-κB. This involvement of ERK and NF-κB transduction factors suggests direct involvement of Toll-like receptors (TLRs) in TLF-induced maturation. We have used MyD88 inhibition and siRNA silencing TLRs on human DCs and mouse TLR-2-knockout cells, to show that TLF triggers the maturation of both human and mouse DCs through TLR-2 and TLR-4.

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“…Use of recombinant lactoferrin offers new therapeutic possibilities for treating bacterial and viral infections (144–147). …”

Section: Future Directionsmentioning

confidence: 99%

Iron metabolism: current facts and future decisions

Tandara

Salamunić

2012

Biochem Med

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Iron metabolism has been intensively examined over the last decade and there are many new players in this field which are worth to be introduced. Since its discovery many studies confirmed role of liver hormone hepcidin as key regulator of iron metabolism and pointed out liver as the central organ of system iron homeostasis. Liver cells receive multiple signals related to iron balance and respond by transcriptional regulation of hepcidin expression. This liver hormone is negative regulator of iron metabolism that represses iron efflux from macrophages, hepatocytes and enterocytes by its binding to iron export protein ferroportin. Ferroportin degradation leads to cellular iron retention and decreased iron availability. At level of a cell IRE/IRP (iron responsive elements/iron responsive proteins) system allows tight regulation of iron assimilation that prevents an excess of free intracellular iron which could lead to oxidative stress and damage of DNA, proteins and lipid membranes by ROS (reactive oxygen species). At the same time IRE/IRP system provides sufficient iron in order to meet the metabolic needs.Recently a significant progress in understanding of iron metabolism has been made and new molecular participants have been characterized. Article gives an overview of the current understanding of iron metabolism: absorption, distribution, cellular uptake, release, and storage. We also discuss mechanisms underlying systemic and cellular iron regulation with emphasis on central regulatory hormone hepcidin.

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The role of talactoferrin alfa in the treatment of non-small cell lung cancer

Abstract: The current role of Talactoferrin alpha in the treatment of NSCLC is described and we explore potential future roles for this drug in both early stage and advanced stage disease.

Cited by 15 publications

References 31 publications

On the selectivity and efficacy of defense peptides with respect to cancer cells

On the selectivity and efficacy of defense peptides with respect to cancer cells

Recombinant human lactoferrin induces human and mouse dendritic cell maturationviaToll‐like receptors 2 and 4

Iron metabolism: current facts and future decisions

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