Transfer Factor

Health Care Professional Information

Scientific Name
Transfer Factor
Clinical Summary

Transfer factors are a complex group of more than 200 highly polar, hydrophilic, low molecular weight (less than 12,000 Daltons) proteins produced in small quantities by lymphoid cells (1). Their precise molecular structure has not been determined. They carry with them the parent lymphocyte's delayed-type hypersensitivity and cell-mediated immunity and pass it along to non-immune recipients, and appear to function across species. Transfer factors can be extracted from human or animal white blood cells, cloned lymphocytes grown in vitro, colostrum, and egg yolk. They appear to be well tolerated and in clinical settings have shown some signs of efficacy in treatment of herpes (2), acute infection in children (3), chronic fatigue syndrome (4), and Candidiasis (5). One study showed effectiveness in increasing white blood cells, CD8 lymphocytes and interleukin 2 levels among patients with HIV (6). Transfer factors are ineffective in treating hepatitis (7), multiple sclerosis (8), extrinsic bronchial asthma (9), human warts (10), juvenile rheumatoid arthritis (29), and acne vulgaris (11).
Studies have shown transfer factors ineffective in treating malignant melanoma (12), nasopharyngeal carcinoma (13), bronchogenic carcinoma (14), Hodgkin's disease (15), osteogenic sarcoma (16), and mycosis fungoides (17). In rats, transfer factors were shown to reduce tumor size and increase peripheral blood T-lymphocyte counts (21). Transfer factors show signs of effectiveness in increasing survival rates among patients with Stage I adenocarcinoma of the lung (18) and Stage I cervical cancer (19), but further research is warranted. In a study of children with leukemia, immunization with transfer factors conferred protection against varicella-zoster infection (20).
Overall, there is a paucity of large randomized controlled clinical trials, and a need for further research into the effectiveness of transfer factors.

Purported Uses
  • Cancer
  • Multiple sclerosis
  • HIV/AIDS
  • Herpes and Epstein-Barr virus
  • Hepatitis
  • Asthma
  • Chronic fatigue syndrome
  • Nonbacterial recurrent cystitis
  • Candidiasis
  • Acne vulgaris
  • Warts
Mechanism of Action

Though the exact mechanisms of transfer factors remain unknown, they contain many molecules, some of which act in an antigen-specific manner, while others have been shown to have immunomodulating capabilities (1). Human leukocyte dialysates (DLE) contain low molecular peptides that were characterized in the late 1980s as amino terminal ends of enkephalins. A low molecular weight sub fraction derived from DLE, IMREG-1, has been shown to enhance cell mediated immunity (22). In vitro studies have shown that both cells murine recipients and humans treated for herpes zoster virus infection secrete gamma-interferon in response to transfer factors (23). Studies have also suggested that production of transfer factors, but not the immunologic activities, is regulated by immune response (Ir) genes. (24).

Pharmacokinetics

It is not clear if transfer factors are absorbed following oral consumption. According to a study done in mice, both oral and parenteral administration of transfer factors was equally effective (25).

Warnings

In 2004, the FDA issued a warning to the 4Life Research Company, marketers of the products “4Life Transfer Factor GluCoach,” “BioGenistein Plus,” and “Transfer Factor ReCall” (26). It found the company to be in violation of the Federal Food, Drug and Cosmetic Act, which prohibits the makers of dietary supplements from marketing them as a means of preventing, diagnosing, mitigating, and treating or curing disease.

Another major concern is contamination of transfer factors isolated from cattle that have bovine spongiform encephalopathy (BSE). The BSE causing prions can accumulate in the brain and damage nerve cells.

Adverse Reactions
  • Reported: Fever; tenderness, pain and swelling when injected. (8)(12)(27)(28)
Literature Summary and Critique

Goldenburg GJ, et al. Cooperative trial of immunotherapy for nasopharyngeal carcinoma with transfer factor from donors with Epstein-Barr virus antibody activity. Cancer Treat Rep 1985; 69(7-8): 761-7.
A prospective randomized double-blind trial evaluated the effect of immunotherapy with transfer factor as an adjunct to radiotherapy of patients with Stage III nasopharyngeal carcinoma (NPC). One hundred patients were randomized to receive either radiotherapy alone or radiotherapy along with an 18-month course of transfer factor immunotherapy. Patients were followed for at least five years, and no significant difference in disease-free survival or survival was noted between the two groups.

Fujisawa T, et al. Randomized controlled trial of transfer factor immunochemotherapy as an adjunct to surgical treatment for primary adenocarcinoma of the lung. Jpn J Surg 1984; 14(6): 452-8.
One hundred and two patients with primary resected adenocarcinoma of the lung were randomly assigned to a treatment group (transfer factor) and a control group (placebo). The treatment group had significantly higher survival rates than the control group in Stage I cases, while there was no significant difference between groups in patients in stages II, III and IV.

Wagner G, et al. Transfer factor for adjuvant immunotherapy in cervical cancer. Cancer Detect Prev Suppl 1987; 1: 373-6.
In a prospective randomized double-blind study of 60 patients with invasive cervical cancer, one group was treated with transfer factor derived from leukocytes of the patients' husbands, while the control group was treated with placebo. Survival rates among members of the treatment group were significantly higher than those of the control group within the first two years after radical hysterectomy. When the collectives were subdivided, significant differences were found in patients under age 35 and in patients with Stage I disease.

Whyte RI, et al. Adjuvant treatment using transfer factor for bronchogenic carcinoma: long-term follow-up. Ann Thorac Surg 1992; 53(3): 391-6.
Between 1976 and 1982, 63 patients who underwent pulmonary resection, mediastinal lymph node dissection and, in some cases, mediastinal irradiation, were randomized into two groups. The treatment group received transfer factor at three-month intervals after operation, while the control group received saline solution at identical intervals. The two-year, five-year and 10-year survival rates in patients receiving transfer factor were not statistically significant when compared with the survival rates of the control group, though the differences between the groups were large enough to merit further research.

References
  1. Rozzo SJ, Kirkpatrick CH. Purification of transfer factors. Mol Immunol. Feb 1992;29(2):167-182.
  2. Estrada-Parra S, Nagaya A, Serrano E, et al. Comparative study of transfer factor and acyclovir in the treatment of herpes zoster. Int J Immunopharmacol. Oct 1998;20(10):521-535.
  3. Jose DG, Ford GW. Therapy with parent's lymphocyte transfer factor in children with infection and malnutrition. Lancet. Feb 7 1976;1(7954):263-266.
  4. De Vinci C, Levine PH, Pizza G, et al. Lessons from a pilot study of transfer factor in chronic fatigue syndrome. Biotherapy. 1996;9(1-3):87-90.
  5. De Vinci C, Pizza G, Cuzzocrea D, et al. Use of transfer factor for the treatment of recurrent non-bacterial female cystitis (NBRC): a preliminary report. Biotherapy. 1996;9(1-3):133-138.
  6. Raise E, Guerra L, Viza D, et al. Preliminary results in HIV-1-infected patients treated with transfer factor (TF) and zidovudine (ZDV).Biotherapy. 1996;9(1-3):49-54.
  7. Ellis-Pegler R, Sutherland DC, Douglas R, Woodfield DG, Wilson JD. Transfer factor and hepatitis B: a double blind study.Clin Exp Immunol. May 1979;36(2):221-226.
  8. Fog T, Pedersen L, Raun NE, et al. Long-term transfer-factor treatment for multiple sclerosis. Lancet. Apr 22 1978;1(8069):851-853.
  9. Valdes Sanchez AF, Martin Rodriguez OL, Lastra Alfonso G. [Treatment of extrinsic bronchial asthma with transfer factor]. Rev Alerg Mex. Sep-Oct 1993;40(5):124-131.
  10. Stevens DA, Ferrington RA, Merigan TC, Marinkovich VA. Randomized trial of transfer factor treatment of human warts. Clin Exp Immunol. Sep 1975;21(3):520-524.
  11. Ashorn R, Uotila A, Kuokkanen K, Rasanen L, Karhumaki E, Krohn K. Cellular immunity in acne vulgaris during transfer factor treatment. Ann Clin Res. 1985;17(4):152-155.
  12. Miller LL, Spitler LE, Allen RE, Minor DR. A randomized, double-blind, placebo-controlled trial of transfer factor as adjuvant therapy for malignant melanoma.Cancer. Apr 15 1988;61(8):1543-1549.
  13. Goldenberg GJ, Brandes LJ, Lau WH, Miller AB, Wall C, Ho JH. Cooperative trial of immunotherapy for nasopharyngeal carcinoma with transfer factor from donors with Epstein-Barr virus antibody activity. Cancer Treat Rep. Jul-Aug 1985;69(7-8):761-767.
  14. Whyte RI, Schork MA, Sloan H, Orringer MB, Kirsh MM. Adjuvant treatment using transfer factor for bronchogenic carcinoma: long-term follow-up. Ann Thorac Surg. Mar 1992;53(3):391-396.
  15. Hancock BW, Bruce L, Sokol RJ, Clark A. Transfer factor in Hodgkin's disease: a randomized clinical and immunological study. Eur J Cancer Clin Oncol. May 1988;24(5):929-933.
  16. Gilchrist GS, Ivins JC, Ritts RE, Jr., Pritchard DJ, Taylor WF, Edmonson JM. Adjuvant therapy for nonmetastatic osteogenic sarcoma: an evaluation of transfer factor versus combination chemotherapy. Cancer Treat Rep. Feb 1978;62(2):289-294.
  17. Thestrup-Pedersen K, Grunnet E, Zachariae H. Transfer factor therapy in mycosis fungoides: a double-blind study. Acta Derm Venereol. 1982;62(1):47-53.
  18. Fujisawa T, Yamaguchi Y, Kimura H, Arita M, Shiba M, Baba M. Randomized controlled trial of transfer factor immunochemotherapy as an adjunct to surgical treatment for primary adenocarcinoma of the lung. Jpn J Surg. Nov 1984;14(6):452-458.
  19. Wagner G, Knapp W, Gitsch E, Selander S. Transfer factor for adjuvant immunotherapy in cervical cancer. Cancer Detect Prev Suppl. 1987;1:373-376.
  20. Steele RW, Myers MG, Vincent MM. Transfer factor for the prevention of varicella-zoster infection in childhood leukemia. N Engl J Med. Aug 14 1980;303(7):355-359.
  21. Pineda B, Estrada-Parra S, Pedraza-Medina B, Rodriguez-Ropon A, Perez R, Arrieta O. Interstitial transfer factor as adjuvant immunotherapy for experimental glioma. J Exp Clin Cancer Res. Dec 2005;24(4):575-583.
  22. Sudhir K SR, Sizemore A, Gottleib A. Immunomodulatory components present in IMREG-1, an experimental immunosupportive biologic. Bio/Technology. 1988;6:810-815.
  23. Alvarez-Thull L, Kirkpatrick CH. Profiles of cytokine production in recipients of transfer factors. Biotherapy. 1996;9(1-3):55-59.
  24. Rozzo SJ, Merryman CF, Kirkpatrick CH. Murine transfer factor. IV. Studies with genetically regulated immune responses.Cell Immunol. Aug 1988;115(1):130-145.
  25. Kirkpatrick CH, Hamad AR, Morton LC. Murine transfer factors: dose-response relationships and routes of administration. Cell Immunol. Sep 1995;164(2):203-206.
  26. Letter from FDA. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/CyberLetters/ucm056666.pdf (Accessed June 25, 2007).
  27. Fudenberg HH, Fudenberg HH. Transfer factor: past, present and future. Annu Rev Pharmacol Toxicol. 1989;29:475-516.
  28. Lloyd AR, Hickie I, Brockman A, et al. Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial. Am J Med Feb 1993;94(2):197-203.
  29. Høyeraal HM, Frøland SS, Salvesen CF. No effect of transfer factor in juvenile rheumatoid arthritis by double-blind trial. Ann Rheum Dis. 1978 Apr;37(2):175-9.

 

Consumer Information

How It Works

Bottom Line: Transfer factors have not been shown to treat or prevent cancer.

Transfer factors are a group of proteins produced by cells of immune system. Some studies have shown that transfer factors can be used for treatment of herpes, infections in children, chronic fatigue syndrome, and yeast infections. They may also boost the immune system in patients with AIDS. More research is needed to determine the anticancer effects of transfer factors.

Purported Uses
  • To treat cancer
    Although some studies have shown that transfer factors can have some positive effects in cancer patients, further research is needed to confirm such observations.
  • To treat multiple sclerosis
    This use is not supported by scientific evidence.
  • To treat HIV/AIDS
    One study showed that transfer factors increased the number of white blood cells in patients with AIDS.
  • To treat herpes and Epstein-Barr virus
    Studies have shown some signs of efficacy in treating herpes.
  • To treat hepatitis (inflammation of liver)
    Transfer factors were not effective in treating hepatitis.
  • To treat asthma
    Some studies have shown that transfer factor does not benefit patients with asthma.
  • To treat chronic fatigue syndrome
    Transfer factor was shown to have positive effects in the treatment of chronic fatigue syndrome.
Research Evidence

Cancer treatment
A well designed trial of 168 patients with Stage I or Stage II melanoma found transfer factor ineffective when used after surgery. Within 90 days of surgery, patients began treatment with either transfer factor or placebo. Treatment continued until patients had been disease-free for two years or until metastasis (spread of tumor cells to other parts of the body). Patients in the placebo group had the highest survival rates compared to those on transfer factor.

Another study was done to find out the effect of immunotherapy with transfer factor in addition to radiotherapy in 100 patients with Stage III nasopharyngeal carcinoma (NPC). Patients were randomized to receive either radiotherapy alone or radiotherapy along with an 18-month course of transfer factor. Patients were followed for at least five years, but no significant difference in disease-free survival or survival was observed between the two groups.

Patient Warnings
  • In 2004, the FDA issued a warning to the 4Life Research Company, marketers of the products “4Life Transfer Factor GluCoach,” “BioGenistein Plus,” and “Transfer Factor ReCall” (26). It found the company to be in violation of the Federal Food, Drug and Cosmetic Act, which prohibits the makers of dietary supplements from marketing them as a means of preventing, diagnosing, mitigating, and treating or curing disease.
  • Another major concern is contamination of transfer factors isolated from cattle that have bovine spongiform encephalopathy (BSE). The BSE causing prions can accumulate in the brain and damage nerve cells.
Side Effects
  • Fever
  • Tenderness, pain and swelling following injection
E-mail your questions and comments to aboutherbs@mskcc.org.