IngredientsDialyzable leukocyte extract (DLE), also called "Lawrence transfer factor," is a mixture of low-molecular-weight peptides (below 10 kDa) that are released upon disruption of peripheral blood leukocytes from healthy human subjects. This lymphocyte product is sometimes referred to as "dialyzable leukocyte extract" in the scientific literature due to being an extract from white blood cells undergoing dialysis to remove all molecules larger than approximately 5,000 daltons.
The dialyzable leukocyte extracts are complexes built up by approximately 200 substances that have low molecular weight. DLE are complexes consisting of a large number of low molecular weight substances, and these extracts possess immunomodulatory properties, which are mainly attributed to small peptides with molecular weight of 3.5–6.0 kDa called "transfer factor."
DLE preparations have been derived from several biological sources:
Transfer factors are given as shots or taken by mouth. Several named proprietary preparations exist. Transferon is a human nonspecific DLE manufactured by the National School of Biological Sciences (ENCB), National Polytechnic Institute (IPN), Mexico, at GMP facilities, and is registered by Mexican health authorities as a drug and is commercialized nationally. IMUNOR is an oral biotherapeutic drug that had been developed, registered, and approved in 1997 in the Czech Republic and Slovakia. In certain countries, such as Mexico, China, Cuba, and the Czech Republic, DLEs are registered as drugs.
The standard unit of Transferon is well-defined: one unit of Transferon is a standardized vial containing 2 mg of dialyzed peptides per 5 mL. In a pediatric atopic dermatitis trial, the oral DLE dose used was oral DLE (2 mg/5 mL), administered daily for 5 days and then every 72 hours to complete one month.
Briefly, leukocytes are separated by centrifugation from an immunized or non-immunized donor's anticoagulated globular package; the supernatant is then separated and centrifuged again to remove excess plasma, leaving a package of leukocytes. The leukocytes are then washed repeatedly and the remaining red blood cells and plasma are eluted. About 150 mL of blood are required to obtain 0.5 cm³ of packed leukocytes. After that, the leukocytes are lysed with distilled water or by 7–10 freeze-thaw cycles in saline solution. The product may or may not be subjected to DNase treatment.
In 1949, Lawrence published the successful transfer of late skin sensitivity to tuberculin (PPD) to PPD-negative patients, and in 1952 he successfully transferred sensitivity to partially purified preparations of the streptococcal substance M by the administration of suspensions of leukocyte components released by cell lysis by repeated freezing and thawing or distilled water lysis.
In 1955, Dr. H. Sherwood Lawrence defined the transfer factor, stating that the cell-mediated immune response to antigens (allergens) can be passively transferred by DLE of viable human leukocytes from a donor of immunity to a naïve recipient. He prepared an intracellular extract from circulating leukocytes of patients who had been exposed to tuberculosis (TB) and then injected the leukocyte extract into non-exposed volunteer patients. Using a delayed type hypersensitivity test, Lawrence demonstrated that the immune system of non-exposed patients treated with leukocyte extract could recognize TB and respond to it, as if it had already fought it. Therefore, the immune response to a certain antigen could be "transferred" from one person to another using a leukocyte extract.
The transfer factor was described by Lawrence in 1955, who found that the dialysable extracts of viable human leukocytes can passively transfer delayed-type hypersensitivity (DTH) to allergens from an immune donor to a naïve recipient. The discovery that it is possible to transfer cell-mediated immunity to naïve recipients by leukocyte derivatives gave a new opportunity to medicine.
The immunologic concept supported by extensive experimental data developed by Lawrence in 1949 was that antigen-specific cell-mediated immunity (CMI) found in dialyzable leukocyte extract (DLE) from an individual sensitive to an antigen could then be transferred to an individual not sensitive to the same antigen. His experiments showed that transferring lymphocytes from a PPD-positive donor to a tuberculin-naïve recipient resulted in the conversion of the recipient to skin-test positivity. At a time when the leading thought was that all immunological phenomena were mediated through antibodies, the idea that lymphocytes produced other immunological molecules that could transfer specific immune memory from patient to patient had radical implications for treating a variety of illnesses.
Building on this breakthrough during the 1950s, Lawrence and collaborators extended the findings to other antigens, achieving successful transfer of delayed hypersensitivity to coccidioidin and histoplasmin in non-immune human subjects through similar leukocyte extracts. These experiments confirmed the specificity of the transferred response, as recipients developed skin test reactivity only to the antigens for which the donor extract was prepared, underscoring the targeted nature of the immune information conveyed.
In 1992, Kirkpatrick described and characterized the term "transfer factor" at the molecular level. The concept of DLE as an immunomodulatory therapeutic has been used in human and veterinary medicine for several decades, particularly in countries where it achieved formal drug registration status, including Mexico, China, Cuba, and parts of Eastern Europe.
The dialyzable leukocyte extracts are complexes built up by approximately 200 substances that have low molecular weight. DLE have immunomodulatory properties, which are due to small peptides—the "transfer factor" (TF). The rest of the components in the extracts have different biochemical and immunological properties and contribute to the immunomodulatory effect carried by TF.
Transfer factor, the main component of the DLE, has a molecular weight of 3.5–6.0 kDa. It consists of small peptides and oligoribonucleotides. The ribonucleotide is attached to the amino terminus of the peptide. The specific activity of TF is due to the peptides weighing 5.0 kDa.
DLEs of human and animal origin typically consist of various biologically active components, which include cyclic nucleotides, nicotinamide, purine bases, histamine, ascorbates, prostaglandins, serotonin, amino acids, proteins, and others.
A study by Myles et al. identified a DLE isolated from an established CD8+ T cell line capable of transferring antigen-specific immunity. The DLE contains a portion of the beta chain of the T cell receptor and additional nucleotide and protein factors that are being subjected to further modern biochemical analysis.
Sinha et al. in 1988 identified two immunologically active peptides in human DLE, Tyr-Gly and Tyr-Gly-Gly, which in turn are part of what was termed "IM-REGe1": a low-molecular weight fraction of human leukocyte dialysates with potential immunostimulatory activity.
"Transferon Oral" is a peptide-derived product with immunomodulatory properties obtained from the lysis and dialysis of human buffy coat; its active pharmaceutical ingredient, generically known as Dialyzable Leucocyte Extract, is a mixture of peptide populations with reproducible proportions among batches. Proteomic analysis indicates that one TF product is a complex set of oligo- and polypeptides constituted of 163 different peptides which can potentially act on multiple mechanisms on the immune system pathways.
DLE is derived from different sub-populations of leukocytes, each one with different functions and molecules; therefore the DLE has many biological effects on the immune system, not all of them immunity-transference related.
The complexity of DLE has impeded an extensive characterization of their components, active substances, and biological activities. To the best of researchers' knowledge, there is only one report on the identification of peptide sequences in dialyzable extracts derived from mammalian cells (mice and bovine) as of 2000 (Kirkpatrick, 2000). In that work, Kirkpatrick obtained the sequence of conserved peptides by Edman's degradation sequencing. However, those peptide sequences have not been found in any known proteome to date.
According to different studies, the main mechanism of action of TF is at the level of cell-mediated immunity. Early studies found that TF could transmit the ability to express delayed hypersensitivity reactions (DHRs), as well as cell-mediated immunity, from an individual or donor previously sensitized with an antigen to a non-immune or non-sensitized recipient.
In vitro studies found that T-cells from healthy individuals could produce TNF-α, IL-12 and IL-10 after DLE stimulation, defining monocytes as the main cellular population that produced TNF-α after stimulation with DLE and showing the direct activation of monocytes via TLR2. Based on these and results of several other researchers, it is assumed that DLE possesses oligoribonucleopeptides and fragments of the T-cell receptor; these immunomodulating peptides stimulate the innate immune system by activating monocytes to produce IL-6 and IL-8, but also the adaptive immune system by enhancing the release of IL-2, IFN-γ, and TNF-α from Th1 cells.
The proposed mechanism of action of Transferon is induction of a Th1 immunoregulatory response. Increased Th1 expression in turn represses production of Th2 and its cytokines like IL-4, IL-5, IL-6, and IL-13.
Dialyzable leukocyte extracts activate TLR-2 on monocytes. This finding positions DLE as a ligand for innate immune pattern-recognition receptors, which may explain its broad immunostimulatory activity independent of antigen specificity.
Investigations have explored whether DLE modulates the production of pro-inflammatory cytokines in leukocytes activated by bacterial cell wall components lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN), as well as the effect of DLE on LPS-stimulated endothelial cells, and whether the regulatory effect of DLE on inflammatory mediators is related to modulation of Toll-like receptors (TLRs), NF-κB and cAMP signaling pathways.
In in vitro models, "Transferon Oral" increases the expression of CD80/CD86 and IL-6 levels in LPS-stimulated macrophage-like THP-1 cells, whereas it induces the differentiation of IFN-γ-producing NK CD56+CD16+CD11c+ cells from CD34+ progenitor cells obtained from human umbilical cord.
In vitro research has shown that TF facilitates the ability of lymphocytes to kill cancer cells. Bovine DLE can cause DNA fragmentation in MCF-7 breast cancer cells and can induce the cytotoxic effect and suppression of some proteins that influence apoptosis (TP53, Bag-1, c-Myc, Bax, Bcl-2 and Bad) at the level of mRNA expression in MCF-7 breast cancer cells.
A beneficial fact is that TF lacks viable cells which play a role in graft versus host reactions, is not immunogenic, and contains no histocompatibility antigens.
This is among the most studied clinical applications of DLE. Clinical trials have shown that DLEs mitigate the duration of the acute phase, the frequency of recurrences, and pain in herpes zoster patients better than acyclovir. These effects correlate with increased IFN-γ levels and CD4+ cell counts.
In animal model research used as a quality-control assay: All 27 Transferon batches tested improved the survival of HSV-1-infected mice, wherein average survival rose from 20.9% in control mice to 59.6% in Transferon-treated mice. The activity of Transferon correlated with increased serum levels of IFN-γ and reduced IL-6 and TNF-α concentrations.
Transferon, the parenteral version of "Transferon Oral," increases IFN-γ levels in serum and favors the clinical course in patients with herpes zoster infection when administered by subcutaneous route.
Evidence strength: There is some human clinical evidence for herpes zoster (recurrence rate, severity, duration), and more substantial animal model data for HSV-1. The human trials cited are generally small and not uniformly placebo-controlled; therefore the evidence is preliminary to moderate.
Studies on cellular transfer factor have involved mostly animal models and small human clinical trials. These studies have demonstrated preliminary evidence of immune modulation as well as some clinical benefits in a handful of diseases, but the studies have not been assessed beyond primary sources and the trials should only be considered pre-clinical. A trial investigating its ability to immunize children with leukemia against shingles showed promise in a small number of patients, but represents only one of two placebo-controlled studies.
Evidence strength: Very limited — one small placebo-controlled trial; not sufficient to draw firm conclusions.
A clinical trial of six years of follow-up was carried out using a DLE preparation in asymptomatic HIV patients. Twenty-eight percent of untreated individuals showed disease progression, while only 7% of DLE-treated patients progressed to AIDS. These results indicate that DLE delays disease progression. However, the molecular basis supporting this effect remained unknown.
Evidence strength: This six-year open follow-up study is intriguing but lacks the rigor of a randomized controlled trial (RCT). Evidence is preliminary; no large, well-controlled RCT has confirmed these results.
Research has reviewed the effect and drawbacks of DLE in form of Dialyzable Leukocyte Extracts or Transfer Factors during and following chemotherapy, radiotherapy, drug interactions, and cancer response in different cancers such as metastatic breast cancer, glioma, prostate cancer, osteosarcoma, and others.
Osteosarcoma: When testing a TF preparation (Transferón) as an adjuvant to chemotherapy in patients with osteosarcoma in stages III and IV, Juarez recorded an increase in the number of CD3+ CD8+, CD16+, and CD56+ cells in the blood of the patients. Treatment of patients with osteosarcoma with transfer factor derived from selected donors increased cell-mediated cytotoxicity. It appears that treatment with TF can provide prophylaxis against metastases when administered to patients without clinically apparent metastases at the time of surgical removal of the primary tumor.
Prostate Cancer: Pizza et al. conducted a follow-up investigation ranging from 1 to 9 years. Fifty patients with prostate cancer unresponsive to conventional therapy were treated with TF. In 44% of them, a beneficial effect was observed (higher survival rates). In murine models, "Transferon Oral" (1–25 μg/kg) reduces tumor growth and metastasis in a murine prostate cancer model.
Lung Cancer: Lung cancer patients using TF demonstrated longer survival rate. (This citation reflects reported data from a small clinical series; controlled trial data are lacking.)
Breast Cancer: DLE increases the percentage of apoptotic tumor cells and the percentage of tumor tissue expressing Th1 cytokines. This study showed the benefits of combining TF with chemotherapy because of the synergic effect, suggesting that chemotherapy doses can be decreased while maintaining the effect of treatment.
Evidence strength: Cancer applications are almost exclusively based on animal models, in vitro studies, and small, uncontrolled or non-randomized clinical reports. No large randomized controlled clinical trials have been published establishing efficacy in any specific cancer. These data are exploratory and hypothesis-generating only.
As the proposed mechanism of action of TF is the increased expression of cytokines of the Th1 phenotype, and because these can inhibit the expression of Th2 cytokines or atopic phenotype, it would be expected that DLE would be useful for treating allergic diseases.
To investigate efficacy and safety of Dialyzed Leukocyte Extracts (DLE) as adjuvant therapy for moderate atopic dermatitis (AD), a double-blind, placebo-controlled, randomized, single-center clinical trial was conducted. Fifty-eight pediatric patients with moderate AD were enrolled and randomized into two groups: conventional treatment plus oral DLE (2 mg/5 mL), daily for 5 days and then every 72 hours to complete one month; or conventional treatment plus placebo at the same dosage and administration. A significant clinical improvement was observed since day 14 with both conventional treatment and conventional treatment plus DLE therapy, but no significant differences in the main clinical outcome measures were found between groups.
Evidence strength: One small double-blind RCT in pediatric atopic dermatitis found no significant superiority of adding DLE over conventional therapy alone. Evidence is weak and not supportive of DLE specifically for this indication from the available controlled trial.
The treatment with TF leads to restoration of the expression of the Th1 cytokine pattern, whereas the increase of delayed type hypersensitivity leads to inhibition of bacterial proliferation and animal survival, as shown in mouse tuberculosis models. Treatments with TF preparations to patients suffering from leprosy were performed for a fairly long time (over 40 years). Improvement in the condition of patients was achieved, but the results were not convincing. TF preparations were obtained and tested against chronic mucocutaneous candidiasis, coccidioidomycosis, and fungal keratitis.
Evidence strength: Weak to preliminary; mostly animal and small uncontrolled clinical series. Leprosy data specifically were inconclusive.
TF in Hepatitis C cases stimulated Th1, which helps in viral particle clearing. Human clinical evidence remains limited to small, non-randomized reports.
Evidence strength: Very preliminary; inadequate controlled data exist.
A 2025 murine study explored the combination of human DLE with the antiparasitic drug albendazole: HLE combined with albendazole enhanced larval clearance and suppressed 14-3-3 gene expression in larvae in a murine model of Mesocestoides vogae infection. This represents current preclinical exploration but has no human translation yet.
Transfer factors are given as shots or taken by mouth. Specific dosages reported in the scientific literature include:
The most common adverse event (AE) observed with DLE (Transferon) was headache in 15.7% of patients, followed by rash in 11.4%, increased disease-related symptomatology in 10%, rhinorrhea in 7.1%, cough in 5.7%, and fatigue in 5.7% of patients. 63% of adverse event presentation occurred from day 1 to day 4 of treatment with Transferon, and mean time to resolution of adverse events was 14 days. In 23 cases, therapy was stopped because of adverse events, and no serious adverse events were observed in this study. Transferon induced low frequency of nonserious adverse events during adjuvant treatment.
Side effects include fever and swelling and pain at the injection site.
Human-derived transfer factor appears to be safe for use for up to two years, and bovine-derived cellular (from blood sources) transfer factor for up to three months. Long-term oral administration of colostrum-derived transfer factors has been shown to be safe.
The injectable form of transfer factor from humans has been evaluated in children when given for up to 6 years. Transfer factor from cows has been evaluated in children when given by mouth for up to 6 months.
Transfer factors are contraindicated for women who are pregnant or breastfeeding.
When human- and bovine-derived transfer factor are generated from blood cells, they carry the potential for blood-borne disease such as HIV/AIDS and Hepatitis C.
Concern has been raised over the possibility of catching Bovine spongiform encephalopathy (Mad Cow Disease) or other diseases from animal blood-derived products. There is some concern about the possibility of catching "mad cow disease" (bovine spongiform encephalitis, BSE) or other diseases from products that come from animals. "Mad cow disease" has not been transmitted by transfer factor, but it is probably wise to avoid animal products from countries where mad cow disease has been found.
No mutagenic effect was observed in one product analysis, and the LDâ‚…â‚€ was 5,000 mg/kg body weight, which accounts for a safe product to be used by the oral route, with potential benefits for the immune system.
A comprehensive physicochemical characterization of DLE is necessary due to its highly complex composition, and the development of multiple analytical methods is essential for the qualitative specification of DLE drug products consisting of a complex mixture of peptides and nucleotides. Standardization remains an ongoing challenge across different manufacturers and preparations. Their complexity has impeded an extensive characterization of their components, active substances, and biological activities.
Despite a small modicum of successes, transfer factor generated from human blood (human-derived), cow spleen (bovine-derived), or mouse spleen (murine-derived) is not in routine clinical use today. Instead, transfer factors derived from cow colostrum and/or chicken egg yolks are used predominantly in commercial contexts today.
Health conditions that Dialyzable leukocyte extract may help support.
Body systems that Dialyzable leukocyte extract may help support.
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