Functional homology of the sex-factor and resistance transfer factors.
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Drug Resistance, Microbial↗
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Susceptibility of murine transfer factor to dimerized ribonuclease A.
Dialyzable transfer factor was prepared from the spleens of CF1 mice actively sensitized with killed Coccidioides immitis antigen. The transfer factor was administered to normal mice either intraperitoneally or into the hind footpads. The recipient mice were tested for reactivity to the coccidioides antigen and to Candida albicans antigen by means of the footpad swelling test. The transfer factor conferred antigen-specific reactivity upon normal recipient mice when given by the intraperitoneal and footpad routes. This capacity of the transfer factor was destroyed by in vitro pretreatment with dimerized ribonuclease A, an enzyme active against double-stranded, as well as single-stranded, ribonucleic acid. In contrast, monomeric ribonuclease A, which is active against only single-stranded ribonucleic acid under the conditions used here, was without effect upon the transfer factor. These data provide evidence that murine transfer factor contains ribonucleotides that are essential for immunological activity. In addition, the data are consistent with the hypothesis, advanced by others, that the ribonucleotides may be double-stranded or uniquely looped configurations.
Animals↗
Transfer factor II: results of therapy.
Transfer factor is a dialyzable extract of sensitized leukocytes, which transfers reactivity from skin test-positive donors to skin test-negative recipients. Transfer factor supplied by our laboratory has been used therapeutically to induce cellular immunity in 78 patients around the world. Many patients received multiple doses of transfer factor ranging from 1 unit given every 6 months for 3 years to 1 unit every week for 6 months to as much as 8 units per week for a brief period. A total of 299 units of transfer factor have been given. Diseases in which transfer factor appeared to cause improvement include the Wiskott-Aldrich syndrome, severe combined immunodeficiency disease, mucocutaneous candidiasis, chronic active hepatitis, coccidioidmycosis, dysgammaglobulinemia, Behcet disease, aphthous stomatitis, linear morphea, familial keratoacanthoma and malignancy.
Amphotericin B↗
Transfer factor.
A workshop on transfer factor, sponsored by the Immunology, Allergic and Immunologic Diseases Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, was held in Bethesda, Maryland, on February 25, 1981. The purpose of the meeting was two-fold: (1) to review the state of the art of transfer factor and (2) to suggest future directions for research in this area, specifically in regard to the prophylactic use of transfer factor for varicella-zoster in leukemic children.
Child↗
Transfer factor I: methods of therapy.
Transfer factor was first discovered by Lawrence in 1955, but was not used therapeutically until 1969 when we reported its use in a Wiskott-Aldrich patient. Since that time, it has been used in a wide variety of disorders related to defects in cellular immunity, infectious diseases, and malignant diseases. This report describes our experience with transfer factor. Report number I discusses rationale for patient selection, procedures for transfer factor therapy, procedures for monitoring the efficacy of therapy, untoward effects of therapy, and experience with transfer factor therapy in severe combined dual system deficiency disorder. The results of our study on transfer factor therapy indicate that it is capable of inducing a clinically acceptable level of cell-mediated immunity in approximately 50% of patients with a variety of immunodeficiency disorders. It also appears to be a useful adjunct to chemotherapy, and may possibly act synergistically with transplanted fetal thymocytes to produce a constantly regenerating specifically competent source of T lymphocytes, thereby obviating the need for bone marrow transplant for severe combined dual system deficiency disorder.
Antibody Formation↗
Effect of transfer factor on lymphocyte function in anergic patients.
Dialyzable transfer factor, obtained from frozen-thawed peripheral blood leukocytes from a single donor, was given to five anergic patients with chronic mucocutaneous candidiasis. Studies of immunological responses including delayed cutaneous hypersensitivity, in vitro antigen-induced thymidine incorporation, and production of macrophage migration inhibition factor (MIF) were conducted both before and after injection of transfer factor. Before transfer factor, none of the patients had delayed skin responses to any of the natural antigens studied. Their lymphocytes did not produce MIF after exposure to antigens in vitro and only one patient showed increased thymidine incorporation when his lymphocytes were cultured with candida and streptokinase-streptodornase (SK-SD). After injection of transfer factor, four patients developed delayed skin responses to antigens to which the donor was sensitive; no recipient reacted to an antigen to which the donor was nonreactive. Lymphocytes from recipients produced MIF when cultured with antigens that evoked positive delayed skin tests. Only one patient developed antigen-induced lymphocyte transformation and this response occurred only intermittently. Attempts to sensitize three of the patients with the contact allergen, chlorodinitrobenzene, both before and after transfer factor, were unsuccessful. The fifth patient, a 9-yr old boy with an immunologic profile similar to the Nezelof syndrome, did not become skin test-reactive or develop positive responses to the in vitro tests. These findings suggest that transfer factor acts on the immunocompetent cells that respond to antigens with lymphokine production, but has little, if any, effect on cells that respond to antigens by blastogenesis. The failure to sensitize the subjects with chlorodinitrobenzene illustrates the specificity of the immunologic effects of transfer factor, and implies that it does not function through nonspecific, adjuvant-like mechanisms. Failure of transfer factor to produce positive skin tests or MIF production in a patient with Nezelof's syndrome may be evidence that lymphokine-producing cells are thymus derived.
Adult↗
Immunologic specificity of transfer factor.
This study examined the immunologic specificity of transfer factor using a chromatographically purified transfer factor preparation. The specificity of transfer was examined utilizing immunity to keyhole limpet hemocyanin (KLH) and tuberculin. Transfer factor prepared from a donor immune to KLH successfully transferred KLH skin test reactivity to 10 out of 10 recipients. In contrast, comparable amounts of transfer factor from two donors not immune to KLH failed to transfer immunity to KLH in 11 recipients despite evidence for successful transfer of tuberculin reactivity. Unlike prior studies with a variety of antigens, the immunity to KLH in recipients of KLH immune transfer factor appeared comparable to that of the donor since both could be elicited with the same skin test antigen dose. These observations indicate that transfer factor can initiate a specific immune response to an antigen not previously encountered by the recipient and that in certain circumstances this immune response can be comparable to that of the donor. These observations on specificity and potency of transfer factor have important implications for the clinical use of this material.
Antibody Specificity↗
Transfer of delayed hypersensitivity in mice to microbial antigens with dialyzable transfer factor.
Dialyzable Lawrence-type transfer factor was prepared from the spleen cells of CF1 mice inoculated with Coccidioides immitis- and Candida albicans-killed vaccines and with live Mycobacterium tuberculosis vaccine (BCG). These preparations were shown to transfer antigen-specific cell-mediated immunity to naive mice, as measured by the delayed skin test and footpad-swelling methods. Reactivity could be demonstrated when the test antigens were given 24 h after the transfer factor, but not when they were given simultaneously. Coccidioides-specific transfer factor was shown to be sensitive to Pronase and resistant to trypsin and ribonuclease. A preparation of BCG transfer factor was sensitive to snake venom phosphodiesterase.
Animals↗
Properties and activities of transfer factor.
Although there is agreement that transfer factor endows skin test-negative subjects with the ability to develop the delayed allergic responses of the transfer factor donors, there is little direct information on the mechanism of this phenomenon or on the nature of the active components (s). This report reviews some of the known effects of transfer factor or immune responses and inflammation. It is concluded that transfer factor has multiple sites of action, including effects on the thymus, on lymphocyte-monocyte and/or lymphocyte-lymphocyte interactions, as well as direct effects on cells in inflammatory sites. It is also suggested that the "specificity" of transfer factor is determined by the immunologic status of the recipient rather than by informational molecules in the dialysates. Finally, it is proposed that many effects of transfer factor may be due to changes in intracellular cyclic nucleotide content, especially accumulation of cGMP, in immunologically reactive cells.
Antibody Formation↗
[Analysis of the contents of Zn, Cu, Fe, Mn, Co and Ni in thymopeptide and transfer factor biological injections].
Thymopeptide and transfer factor are two common clinic biological preparations, which are used to cure immunodeficiency, low immunofunction or infectious disease caused by virus or fungi owing to their functions of increasing body immunity. In order to discuss the relationship between trace elements and those related diseases, to coordinate sound clinic use of the preparations and to provide productive data on them, atomic absorption spectrophotometry was used to detect the contents of Zn, Cu, Fe, Mn, Co and Ni in thymopeptide and transfer factor biological preparations. Respective contents of detected elements were compared in a statistical way. Results show that Zn and Co contents in thymopeptide were lower than in transfer factor; the contents of Cu, Fe, Mn and Ni, in thymopeptide were higher than in transfer factor. For Zn, Cu, Mn and Co, there was a significant difference between the two biologicam preparations (P<0.01). For Fe and Ni there was a great difference (Q<0.05). The results can provide useful data for sound clinic biological injection to promote immune function, and for increasing or decreasing certain trace elements in preparation.
Clinical Laboratory Techniques↗
Clinical trials of transfer factor in malignancy.
Results of clinical trials of transfer factor therapy in various malignancies have been variable. In non randomized trials, about 300 patients have been evaluated, and clinical benefit has been reported in about 1/3 of the evaluable patients. Results of randomized studies are similarly varied. In some randomized trials, clinical benefits of increased disease free survival and prolonged survival have been claimed. In other studies, transfer factor has been reported to be of no clinical benefit. In a few studies, results suggest patients receiving transfer factor do not do as well as those receiving placebo, although these are only trends, and do not reach the level of statistical significance. There are a number of variables in the design of transfer factor trials, and review of the studies performed to date does not permit a determination of which, if any, of these variables is related to the therapeutic outcome. A variety of tumor types have been evaluated, and it is not clear which, if any, tumors respond to transfer factor. Similarly, the state of disease and prior and concomitant therapy vary widely in these trials and the impact of these variables is unclear. The source and dose of transfer factor also varies. In some studies, attempts have been made to select donors who might have cellular immune reactivity to the tumor being treated, whereas in other studies normal donors have been used. The rationale for the use of normal donors in that the clinical benefit of transfer factor may be related to the non specific immunopotentiating effects of this agent rather than the specific transfer of cellular immunity. Finally, the methods of preparation of transfer factor vary and the products used in various studies cannot be compared by standard biologic or biochemical tests currently available. This review of the literature regarding the clinical effort of transfer factor in malignancy leads to the conclusion that transfer factor might not be an effective therapy of cancer. If it does have efficacy in certain malignancies, it is unlikely that it will alone have dramatic effects in substantial numbers of patients. Perhaps transfer factor may have a role in tumor therapy as an adjuvant to other forms of therapy and as surgery, irradiation, or chemotherapy. In order for the proper evaluation of transfer factor in reproducible comparative studies, it will be necessary to have a standarized reproducible product which can be assessed by appropriate quality control procedures.(ABSTRACT TRUNCATED AT 250 WORDS)
Breast Neoplasms↗
[Technics and applications of transfer factor (author's transl)].
Transfer factor is produced by dialysis of repeatedly frozen and thawed pooled buffy coats of healthy blood donors. However, "specific Transfer Factor" of bacteriological or mycological type, prepared from hyperimmunized donors would be more effective for restoring cellular immunity.
Hematologic Diseases↗
Transfer factor: a murine model.
Transfer factor has been studied extensively in humans, but a satisfactory subprimate model has not been established. Using BALB/c mice immunized with complete Freund adjuvant, we show that a low-molecular-weight substance derived from disrupted spleen cells transferred sensitivity to purified protein derivative (PPD) to recipient nonimmunized BALB/c mice. Transfer was confirmed by footpad swelling to PPD in vivo and by splenic lymphocyte transformation to PPD in vitro. In recipients of transfer factor, an inverse correlation was noted between the splenic lymphocyte response to PPD and to concanavalin A. Material obtained from spleens of saline-treated BALB/c mice did not transfer sensitivity to PPD to recipient mice.
Animals↗
Activities and characteristics of transfer factors.
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 further examine this issue, we have conducted dose-response studies of the delayed-type hypersensitivity reaction in mice 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-IFN, 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.
Administration, Oral↗
Transfer factor.
The understanding of passive transfer of cell mediated-immune responses with transfer factor and other cell free materials has progressed to the point that investigators are seeking the chemical identity of the molecule(s) that are responsible for these effects and are working on their mechanisms of action. In addition, clinical trials are underway that should clarify the potential for use of transfer factor in treatment of infections, neoplastic and autoimmune diseases. This chapter will critically review the past and current data concerning the components of transfer factor and their effects on immunologic and inflammatory reactions. Some of the recently developed animal models will be described and evaluated, and the clinical studies that have provided conclusive data regarding efficacy will be reviewed.
Animals↗
Murine transfer factors: dose-response relationships and routes of administration.
Transfer factors are protein immunomodulators that transfer the ability to express cell-mediated immunity from immunized donors to nonimmune recipients. The effects are antigen-specific. The experiments described in this report are a comparison of the relationship of the route of administration of various transfer factors to the magnitude of the delayed hypersensitivity responses (footpad swelling) to the corresponding antigen in the recipients. Three doses of each of four affinity-purified transfer factor preparations were studied. There were no significant differences in the footpad responses by recipients of either oral or subcutaneous transfer factor. These results support proposals for oral administration of transfer factors in clinical trials.
Administration, Oral↗
[F-like genetic transfer factor pAP42].
Sensitivity of E. coli K-12 cells containing the transfer factor pAP42 to phages was examined to determine the frequency of the test factor transfer from one cell to another one. The data on the phage sensitivity and the frequency of transfer indicate that the test factor is F-like plasmid derepressed by the conjugation function. Study of incompatibility of the transfer factor pAP42 has shown its compatibility with plasmids of all 8 groups of F-incompatibility. This enables one to characterize this factor as a representative of a new FIX group of F-incompatibility.
Coliphages↗
Lymphocyte transformation, IgE and T-cells in eczema vaccinatum treated with transfer factor. A case report.
Transfer factor (TF) was given to intensify the cell-mediated immune reactions in an atopic patient with generalized vaccinia. The patient showed marked reactivity of peripheral blood lymphocytes to stimulation with phytohaemagglutinin and pokeweed mitogen, but also in nonstimulated cultures. However, later tests with mitogen stimulation of lymphocytes indicated a defective cellular defence mechanism. The addition of autologous plasma to lymphocyte cultures depressed the reactivity of PHA-stimulation considerably. Initially, the patient also showed a normal T-lymphocyte count in peripheral blood, but six months after her vaccinia, extremely high serum IgE levels and a decreased percentage of T-lymphocytes was observed. Although an evaluation of the clinical effect of transfer factor injection is difficult, it should be noted that the patient's temperature immediately fell to normal, and her general health improved following treatment.
Adolescent↗