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Biotherapy 1996;9(1-3):13-6
Activities and characteristics of transfer factors.

Kirkpatrick CH
Innovative Therapeutics, Inc. Denver, CC), USA.

This report summarizes three components of our transfer factor research program. Several clinical studies have used oral administration of transfer factor containing materials. Sceptics have rejected these findings by assuming that the acidic and enzymatic environment of the gastrointestinal tract would destroy the factors. To ftirther examine this issue, we have conducted dose-response studies of the delayed-type hypersensitivity reaction in rnice that were given transfer factor either by gavage or subcutaneously. There were no difference in the responses that were related to the route of administration. We conclude that oral route of administration is efficacious and should be used when possible. We have also studied the effects of transfer factors on immune responses by recipients. The details of this research are presented in the paper by Dr. Alvarez-Thull. Briefly, the study showed that recipients of a specific transfer factor responded to the antigen for which the factor was specific by secreting gamma-EFN, but no other cytokines. The structures of transfer factor molecules are unknown. We have developed a process for isolating transfer factors in pure form and we have obtained preliminary data concerning amino acid sequences. Our goal is to obtain the complete primary structure of several transfer factor molecules.

PMID: 8993752, Ul: 97146896

Biotherapy 1996;9(1-3):7-11
Transfer factor in the age of molecular biology: a review.

Dwyer JM Division of Clinical Immunobiology of the Prince Henry and Prince of Wales Hospitals of the University of New South Wales, Sydney, Australia.
Current data suggests that the transferring of immunologically specific information by transfer factor molecules requires interaction with a cell that has been genetically progrannned to be antigen reactive but at the time of interaction is unprimed. Contact with transfer factor molecules would allow a naive recipient, on a first encounter with antigen, to make a secondary rather than a primary immunological response. Transfer factor molecules for each and every antigenic determinant are thus necessary. Transfer factors made from animals or humans are capable of transferring antigen specificity across a species barrier. Even primitive species have cells from which one can make transfer factors. The molecules are, therefore, well conserved and it is reasonable to suggest that they are important for normal immunological functioning. Proposed mechanisms of action must explain the fact that transfer factors obtained from the cells of high responder animals are capable of transferring delayed hypersensitivity to low responder animals while the reverse is not true. Transfer factor molecules are likely to interact with the variable regions of the alpha and/or beta chain of T cell receptors to change their avidity and affinity for antigen in a way that otherwise would only occur after an encounter with antigen. Publication Types: -Review -Review, tutorial

PMID: 899375 1, Ul: 97146895

Biotherapy 1996;9(1-3):1-5
Transfer factor--current status and future prospects.

Lawrence HS, Borkowsky W Department of Medicine, New York University Medical Center, New York, NY 100 16, USA.
We have detected new clues to the composition and function of "Transfer Factor" using the direct Leucocyte Migration Inhibition (LMI) test as an in vitro assay of Dialysates of Leucocyte Extracts (DLE). This approach has revealed two opposing antigen-specific activities to be present in the same > 3500 < 12,000 DA dialysis fraction - one activity is possessed of Inducer/Helper function (Inducer Factor). The opposing activity is possessed of Suppressor function (Suppressor Factor). When non-immune leucocyte populations are cultured with Inducer Factor they acquire the capacity to respond to specific antigen and inhibition of migration occurs. This conversion to reactivity is antigen-specific and dose-dependent. When immune leucocyte populations are cultured with Suppressor Factor their response to specific antigen is blocked and Inhibition of Migration is prevented. Publication Types: -Review – Review, tutorial

PMID: 8993750, Ul: 97146894

Lancet 1981 Jul 18;2(8238):122-4
Treatment of childhood combined Epstein-Barr virus/eytomegalovirus infection with oral bovine transfer factor.

Jones JF, Minnich LL, Jeter WS, Pritchett RF, Fulginiti VA, Wedgwood RJ
An illness lasting for two years, with recurrent fever, rash, abdominal pain, and arthralgia, developed in a four year old boy. He was found to have a combined Epstein-Barr virus and cytomegalovirus (CMV) infection. His symptoms, CMV in his urine, and an absent in vitro lymphocyte response to CMV antigen persisted for two years. After treatment with orally administered bovine transfer factor clinical symptoms and viruria disappeared and specific immunity to CMV developed. Evaluation of this treatment in chronic virus infections is warranted.

PMID: 6113484, LTI: 81219911

Biotherapy 1996;9(1-3):55-9
Profiles of cytokine production in recipients of transfer factors.

Alvarez-Thull L, Kirkpatrick CH Innovative Therapeutics, Inc., Denver, CO, USA. Transfer factors (TF) are proteins that transfer the ability to express cell-mediated immunity from immune donors to non-immune recipients. The mechanisms of these effects have not been defined. The experiments described in this report were undertaken to test the hypothesis that a mechanism through which the beneficial effects of TF are expressed in clinical situation is through "education" of the immune system to produce certain cytokines in response to antigenic stimulation. BALB/c mice were sensitized to Herpes simplexvirus (HSV) either by sublethal systemic or cutaneous infections by administration of a HSV-specific TF. One week later their spleen cells were collected and single cell suspensions were stimulated in vitro with irradiated HSV or concanavatin. A Culture supernatants were collected and assayed for content of U--2, EL-4, IL-10 and EFN-G. Spleen cells from infected mice responded to concanavalin A and to HSV by secreting large amounts of EL-2 and EFN-G, modest amounts of EL-10, and no EL-4. Transfer factor recipients produced similar cytokine profiles in response to concavalin A. These mice, however, responded to HSV by secreting IFN-G, but no EL-2. Thus, TF treatment selectively affects cytokine production in response to antigenic stimulation.

PMID: 8993758, Ul: 97146902

Arch Otolaryngol 1975 Nov;101(11):664-6
Transfer factor: Potential for therapy of malignant diseases.

Neidhart JA, LoBuglio AF
Transfer factor (TF) is a low molecular weight nonantigenic extract of leukocytes that is capable of transferring cell-mediated immunity from an immune individual to a nonimmune individual. Reports of efficacy of transfer factor in immunodeficiency states and chronic infectious diseases, as well as its lack of toxicity, have spurred clinical trials of TF therapy in human malignant diseases. Variables such as donor and patient selection, dose of TF, and use of concurrent therapy have not been explored. Preliminary reports suggest that TF may find a role as adjuvant therapy in human malignant neoplasms.

PMID- 1200907, Ul: 76087317

In Vivo 1994 Jul-Aug;8(4):555- 7
Successful treatment of severe complicated measles with non-specific transfer factor.

Ferrer-Argote VE, Romero-Cabello R, Hernandez-Mendoza L, Arista-Viveros A, Rojo-Medina J, Balseca-Olivera F, Fierro M, Gonzalez-Constandse R Department of Hematology, Hospital General de Mexico, DF, Mexico.
Severe complicated measles has a high mortality rate and no specific treatment. Ten patients with complicated measles - 9 infants with respiratory failure and a 15 year old boy with encephalitis - received immunotherapy with Non-specific Transfer Factor (NTF). The patients had variable degrees of undernourishment and were severely ill when immunotherapy was started. 8/9 cases with respiratory failure were cured. One died of bronchoaspiration while recovering from the measles. The case with encephalitis showed no neurological sequelae two weeks after receiving the last dose of NTF. Treatment of complicated measles with NTF in these patients seemed very effective and deserves ftirther trial.

PMID: 7893983, Ul: 95201208