Apolactoferrin (talactoferrin alfa) / Agennix - LARVOL DELTA

ORAL RECOMBINANT HUMAN LACTOFERRIN (RHLF) ALTERS BOTH MICROBIOME AND METABOLOME TO DECREASE ILEITIS IN TNFΔARE MICE (DDW 2025) - "rhLF treatment resulted in a shift of the balance of pro- and anti-inflammatory T cell populations to favor resolution of gut inflammation. Our data identifies plausible mechanisms for this shift including a change in the luminal microbiome and metabolome."

Preclinical • Inflammation • Inflammatory Bowel Disease

Recombinant human holo-lactoferrin in complex with oleic acid suppresses the growth of solid myeloma more efficiently than its apo-form. (PubMed, Biochem Cell Biol) - "Our previous study showed antitumor activity of the complex formed by iron-free recombinant human lactoferrin (apo-recHLF) and oleic acid (1:8 molar ratio) in a model of murine hepatoma 22a inoculated to C3HA mice...I/p injections of apo-recHLF/OA complex did not inhibit the tumor growth. Holo-recHLF used without OA had less pronounced antitumor effect as compared with their complex."

Journal • Hematological Malignancies • Hepatocellular Cancer • Liver Cancer • Multiple Myeloma • Oncology • Solid Tumor

Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia. (PubMed, Mol Med) - "In contrast, recombinant human lactoferrin promotes neuronal proliferation by upregulating ERK 1 and 2 phosphorylation and attenuates LPS-induced neuronal injury and microglial activation by inhibiting the activation of Toll-like receptor 4-nuclear factor-kappa B pathway in vitro. Our findings suggest that lactoferrin intake during lactation protects neurons by regulating microglial activation, thereby effectively reducing depressive symptoms in adults."

Adverse events • Journal • CNS Disorders • Depression • Inflammation • Psychiatry • BDNF • TLR4

Structural characteristics and antioxidant activity of binary compounds formed by covalent modification of plant derived recombinant lactoferrin (OsrhLF) with four typical carbohydrates. (PubMed, Food Chem) - "In this study, structural characteristics and antioxidant activity of binary compounds formed by covalent modification of plant derived recombinant human lactoferrin (OsrhLF) with four typical carbohydrates including sodium alginate (SA), maltodextrin (Mal), pectin (Pec), and lactose (Lac)...Compared with OsrhLF, the thermal denaturation temperatures of H-OsrhLF-Mal and H-OsrhLF-Lac increased by 56.8 °C and 58.4 °C, respectively. OsrhLF exhibited superior surface hydrophilicity and thermal stability compared to bLF, with Mal showing the most significant effect, aiding future functional food applications."

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A Randomized, Double-Blind, Controlled Trial to Assess the Effects of Lactoferrin at Two Doses vs. Active Control on Immunological and Safety Parameters in Healthy Adults. (PubMed, Int J Toxicol) - P=N/A | "Recombinant human lactoferrin (rhLF) is of commercial interest for immune support as a food ingredient...Changes in safety outcomes were similar between groups and within normal ranges. These results show that under the conditions of the protocol, no increased anti-hLF antibodies or adverse events were identified following ingestion of effera™ as a food ingredient at an intake level up to 3.4 g/d in healthy adults (clinicaltrials.gov: NCT06012669)."

Clinical • Journal

Evaluation of the potential food allergy risks of human lactoferrin expressed in Komagataella phaffii. (PubMed, Front Immunol) - "The allergenic risk potential of Helaina recombinant human lactoferrin (rhLF, Effera™), produced in Komagataella phaffii (K...Helaina rhLF was also rapidly digested in simulated gastric fluid and its digestibility profile was comparable to human milk lactoferrin (hmLF), further demonstrating a low allergenic risk and similarity to the hmLF protein. Collectively, these results demonstrate a low allergenic risk potential of Helaina rhLF and do not indicate the need for further clinical testing or serum IgE binding to evaluate Helaina rhLF for risk of food allergy prior to introduction into the food supply."

Journal • Allergy • Food Hypersensitivity • Immunology

The [(bathophenanthroline)3:Fe2+] complex as an aromatic non-polymeric medium for purification of human lactoferrin. (PubMed, J Chromatogr A) - "We describe a non-chromatographic, ligand-free platform for the efficient purification of recombinant human lactoferrin (LF)...We provide evidence that protein capture relies on [cation:π] interactions between the lysine and arginine residues of LF with the fully aromatic [(batho)3:Fe2+] complexes. The use of [metal:chelator] complex aggregates is demonstrated to provide an economical and efficient avenue for LF purification."

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Digestive Profiles of Human Milk, Recombinant Human and Bovine Lactoferrin: Comparing the Retained Intact Protein and Peptide Release. (PubMed, Nutrients) - "No recombinant human lactoferrin (rhLF) is available for commercial food use...Peptides identified in digested hmLF samples strongly correlated with digested rhLF samples (0.86 < r < 0.92 in the gastric phase and 0.63 < r < 0.70 in the intestinal phase), whereas digested bLF samples were significantly different. These findings support the potential for rhLF as a food ingredient for human consumption."

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Workshop Report: A Study Roadmap to Evaluate the Safety of Recombinant Human Lactoferrin Expressed in Komagataella phaffii Intended as an Ingredient in Conventional Foods - Recommendations of a Scientific Expert Panel. (PubMed, Food Chem Toxicol) - "Relevant workshop topics included physicochemical properties of LF, regulatory history of bovine LF and rhLF as food ingredients in the FDA's generally recognized as safe (GRAS) program, and synopses of publicly available studies on the immunogenicity/alloimmunization, immunotoxicology, iron homeostasis, and absorption, distribution, metabolism, and excretion of rhLF. Panelists concluded that the safety study roadmap addresses the unanswered safety questions and the intended safe use of rhLF as a food ingredient and agreed on broad applications of the roadmap to assess the safety and support GRAS of other recombinant milk proteins with immunomodulatory functions."

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Characterization of recombinant human lactoferrin expressed in Komagataella phaffii. (PubMed, Analyst) - "Differential scanning calorimetry investigations into the thermal stability of Helaina rhLF revealed two distinct denaturation temperatures at 68.7 ± 0.9 °C and 91.9 ± 0.5 °C, consistently mirroring denaturation temperatures observed for apo- and holo-hmLF. Overall, Helaina rhLF differed from hmLF in the N-glycans they possessed; nevertheless, the characterization results affirmed that Helaina rhLF was of high purity and exhibited globular structures closely akin to that of hmLF."

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A Review of the Safety Evidence on Recombinant Human Lactoferrin for Use as a Food Ingredient. (PubMed, Food Chem Toxicol) - "However, no human studies evaluated the immunomodulatory potential of rhLF as a measure of safety. Following this review, a roadmap outlining preclinical and clinical studies with relevant safety endpoints was developed to address the unanswered safety questions."

Journal • Review

Dose Range-Finding Toxicity Study in Rats With Recombinant Human Lactoferrin Produced in Komagataella phaffii. (PubMed, Int J Toxicol) - "Quantitative LF levels were also analyzed as an indication of bioavailability. Overall, administration of Helaina rhLF by once daily oral gavage for 14 days was well tolerated in rats at levels up to 2000 mg/kg/day, or 57 × Helaina's intended commercial use in adults, and indicating that a high dose of 2000 mg/kg/day is appropriate for future definitive toxicology studies."

Journal • Preclinical • Hematological Disorders

Study of pH and Thermodynamic Parameters via Circular Dichroism Spectroscopy of a Recombinant Human Lactoferrin. (PubMed, Molecules) - "Thermodynamic parameters such as ΔH, ΔS and Tm were calculated and compared with commercial human lactoferrin. We propose the potential use of CD and thermodynamic parameters as a criterion in the production of recombinant proteins to be used in the production of specialized recombinant proteins."

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New Horizons of Covalent Complex of Plant-Derived Recombinant Human Lactoferrin (OsrhLF) Combined with Different Polyphenols: Formation, Physicochemical Properties, and Gastrointestinal Fate. (PubMed, J Agric Food Chem) - "LF-polyphenol emulsions significantly enhanced the photochemical stability and bioavailability of lycopene and achieved effective encapsulation and protection of lycopene compared to free lycopene, and the OsrhLF-EGCG reached 58.94% lycopene bioavailability. In short, OsrhLF does not differ much from bLF in terms of physicochemical properties and has a strong potential in the field of dietary supplements."

Journal • Gastrointestinal Disorder

Expressing recombinant human lactoferrin with antibacterial activity in Nicotiana benthamiana. (PubMed, Plant Biotechnol (Tokyo)) - "Purified plant-derived rhLF possesses antibacterial activity that inhibits the growth of Escherichia coli. These results indicated that rhLF containing antimicrobial activity can be produced in N. benthamiana using the Tsukuba system."

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Fragmented antibodies in non-small cell lung cancer: a novel nano-engineered delivery system for detection and treatment of cancer. (PubMed, Drug Discov Today) - "When combined with functional nanocarriers, antibody fragments can target cancer cells while offering improved efficacy and fewer off-target effects. We discuss current topics of interest including anti-CTLA-4 mAbs, Talactoferrin alfa (TLF), and the CYFRA 21-1 biomarker, with brief insights into its novel detection system."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

In vitro prebiotic activity of rhLf and galactooligosaccharides on infant intestinal microbiota. (PubMed, Nutr Hosp) - "despite the importance of the batch culture fermentation technique in uncovering the prebiotic activity of food ingredients, it is not useful for detecting the prebiotic nature of Lf due to its nature as a protein. Thus, Lf maybe shows its prebiotic activity on the gut microbiota through other mechanisms."

Journal • Preclinical

Colostrum Proteins in Protection against Therapy-Induced Injuries in Cancer Chemo- and Radiotherapy: A Comprehensive Review. (PubMed, Biomedicines) - "A majority of the reported investigations was performed with bovine colostrum (BC) and native bovine or recombinant human lactoferrin (LF), applied alone, in nutraceutics or in combination with probiotics. Apart from reducing side effects of the applied therapeutics, radiation and surgical procedures, BC and LF augmented their efficacy and improved the wellness of patients. In conclusion, colostrum and colostrum proteins, preferably administered with probiotic bacteria, are highly recommended for inclusion to therapeutic protocols in cancer chemo- and radiotherapy as well as during the surgical treatment of cancer patients."

Journal • Review • Oncology

Human Lactoferrin Synergizes with Etoposide to Inhibit Lung Adenocarcinoma Cell Growth While Attenuating Etoposide-Mediated Cytotoxicity of Human Endothelial Cells. (PubMed, Biomedicines) - "The aim of this study was to evaluate the effect of recombinant human lactoferrin (rhLf) in combination with etoposide on anticancer activity in human lung adenocarcinoma cells. The calculated dose reduction index indicated that the combination treatment reduced a 10-fold of etoposide dose to achieve the same anticancer effect. Our data demonstrate that rhLf enhanced the anticancer activity of etoposide and diminished etoposide-induced cytotoxic effect in endothelial cells."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Recombinant Human Lactoferrin Augments Epirubicin Chemotherapy in Solid Ehrlich Carcinoma Bearing Mice. (PubMed, Curr Drug Saf) - "Recombinant human lactoferrin exhibited potential anticancer and immuno-enhancing properties in mice with breast cancer. Co-treatment with rhLF and EPI proved to be a promising strategy in cancer treatment."

Journal • Preclinical • Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • IL18 • MAPK8 • TP53

Lactoferrin Induces Erythropoietin Synthesis and Rescues Cognitive Functions in the Offspring of Rats Subjected to Prenatal Hypoxia. (PubMed, Nutrients) - "The protective effects of recombinant human lactoferrin rhLF (branded "CAPRABEL™") on the cognitive functions of rat offspring subjected to prenatal hypoxia (7% O, 3 h, 14th day of gestation) have been analyzed...Apo-rhLF injected to rat dams either during pregnancy or nurturing the pups was able to rescue cognitive deficits caused by prenatal hypoxia and improve various types of memory both in young and adult offspring when tested in the radial maze and by the Novel Object Recognition (NOR) test. The data obtained suggested that the apo-form of human LF injected to female rats during gestation or lactation protects the cognitive functions of their offspring impaired by prenatal hypoxia."

Journal • Preclinical • Cognitive Disorders

Genetically engineered pH-responsive silk sericin nanospheres with efficient therapeutic effect on ulcerative colitis. (PubMed, Acta Biomater) - "Here, we report an effective strategy to fabricate silk sericin nanospheres systems for the delivery of recombinant human lactoferrin (SS-NS-rhLF)...The fabricated SS-NS-rhLF showed identical spherical morphology, stable structure, sustainable rhLF release, efficient cell uptake and negative charge in an environment of pH above 5.5, thus realized the specific targeting to the positively charged colonic sites to treat UC mice through oral administration. The therapeutic effect of SS-NS-rhLF with a low rhLF dose in the UC mice was comparable to the high dose of free rhLF treatment in solution form, suggesting that the SS-NS-rhLF is a promising system for colitis treatment."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

Recombinant Human Lactoferrin Reduces Inflammation and Increases Fluoroquinolone Penetration to Primary Granulomas During Mycobacterial Infection of C57Bl/6 Mice. (PubMed, Arch Immunol Ther Exp (Warsz)) - "Increased drug penetration was accompanied by retention of endothelial cell integrity. Immunohistochemistry revealed altered patterns of M1-like and M2-like phenotypic cell localization post infectious challenge, with increased presence of M2-like markers found evenly distributed throughout regions of pulmonary inflammatory foci in rHLF-treated mice."

Journal • Preclinical • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Lactoferrin modified by hypohalous acids: Partial loss in activation of human neutrophils. (PubMed, Int J Biol Macromol) - "Here we compared the effects of recombinant human lactoferrin (rhLTF) and its halogenated derivatives (rhLTF-Cl and rhLTF-Br) on functional responses of neutrophils...Furthermore, all rhLTF forms interfered with PMA- and ionomycin-induced formation of neutrophil extracellular traps. Thus, halogenative modification of LTF is one of the mechanisms involved in modulating a variety of signaling pathways in neutrophils to control their pro-inflammatory activity."

Journal • Immunology • Inflammation • MPO

Kinetic investigation of protein adsorption into polyelectrolyte brushes by quartz crystal microbalance with dissipation: The implication of the chromatographic mechanism. (PubMed, J Chromatogr A) - "In this work, we use quartz crystal microbalance with dissipation to in situ investigate adsorption kinetics of γ-globulin and recombinant human lactoferrin on poly(3-sulfopropyl methacrylate) (pSPM) sensors prepared via atom transfer radical polymerization...Furthermore, the influence of buffer pH and salt concentration further validated the ion exchange characteristics of protein adsorption into pSPM brushes. The research provided a variety of in situ evidence of protein binding and conformation evolution in pSPM brushes and elucidated mechanism of protein adsorption in pSPM brushes."

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