Transfer Factor Therapy Research Articles

A Case of Varicella Pneumonia Treated With Transfer Factor

To the Editor.— We read the case report of disseminated cryptococcosis treated with transfer factor written by Gross et al (240:2460, 1978). We experienced similar results with transfer factor therapy for a disseminated infection involving both skin and lungs that also was not amenable to antibiotic therapy. Report of a Case.— An 11-year-old boy was being followed up for chronic neutropenia and recurrent otitis media at Oklahoma Children's Memorial Hospital and Grady Memorial Hospital. Immunologic evaluation of this patient's condition disclosed decreased serum immunoglobulin level, absence of isoagglutinins, and normal phytohemagglutinin-induced lymphocyte transformation, but absence of delayed hypersensitivity to a battery of common antigens and an average leukocyte count of less than 100/cu mm. With no previous history of the disease, the patient had shown development of typical vesicles of chickenpox. For the first four days of his illness, he experienced a successive crop of vesicles in excess of that

A double-blind evaluation of transfer factor therapy of HB sAg-positive chronic aggressive hepatitis: Preliminary report of efficacy

A controlled, prospective, double-blind trial of transfer factor in chronic aggressive hepatitis was carried out. This report presents the results obtained from study of the nine HB sAg-positive subjects who were included in the trial. Transfer factor was prepared from adults who had recovered from acute hepatitis B or from acute non-B viral hepatitis and was administered to five HB sAg-positive subjects. Four HB sAg-seropositive subjects received placebo. Percutaneous liver biopsy was performed at the beginning and at the conclusion of the 10-week study period; biochemical and clinical parameters were monitored throughout. Cell-mediated immunity was assessed at the beginning and at the end of the study period. Four of five transfer factor recipients showed moderate or marked improvement in hepatic histology, clinical status, and serum transaminase levels, while none of four placebo recipients demonstrated improvement. The difference in response between the two groups was significant ( P = 0.048). No consistent changes in in vivo or in vitro correlates of cell-mediated immunity were demonstrated. No adverse effects were noted among transfer factor recipients. These data suggest that transfer factor may be of benefit in chronic aggressive hepatitis associated with HB sAg. Additional studies appear to be indicated to delineate the mode of action of transfer factor as well as the role that such immunotherapy should play in the management of patients with this disorder.

Hyperimmunoglobulin E syndrome: Response to transfer factor and ascorbic acid therapy

This report presents the case history of a 29-year-old man with hyperimmunoglobulin E syndrome and the successful treatment with transfer factor and ascorbic acid. The patient presented with a marked defect in the ability of his lymphocytes to respond to mitogens, in skin test response to DNCB challenge and other recall antigens, and a variety of in vitro granulocyte function defects. The presence of a serum inhibitor to lymphocyte and granulocyte function was found. This individual had multiple episodes of mucocutaneous candidiasis and staphylococcal infections. Clinical improvement was evident after transfer factor and ascorbic acid treatment. Many of the in vitro functions also returned to normal.

Preliminary results of transfer factor therapy of persistant cutaneous leishmania infection

Three patients with persistent cutaneous leishmania infection of 8-, 14- and 30-year duration, respectively, and with demonstrable delayed hypersensitivity to leishmania antigens were treated with leishmania-specific transfer factor prepared from healthy donors with a previous history of cutaneous leishmania infection. The cutaneous lesions healed completely in all three cases. The total dose of transfer factor required to achieve healing was much higher than the dose used by other investigators. The results justify a further clinical trial to determine the therapeutic effectiveness of transfer factor in cutaneous leishmaniasis. Further, because the infective agent is neither ubiquitous nor homogeneous, cutaneous leishmania infection in man offers a unique opportunity for a double blind study aimed at evaluating the therapeutic usefulness of transfer factor in human intracellular infections and further analytic studies to determine both the in vivo and in vitro specificity of transfer factor.

Disseminated Cryptococcus Treated With Transfer Factor

Cardiac toxic reactions and pulmonary consolidation in the left lower lobe developed in a patient who was receiving amphotericin B therapy for cryptococcal meningitis. Following surgical resection of the lobe, multiple subcutaneous cryptococcal abscesses appeared. Flucytosine administered intravenously failed to eradicate the lesions. Transfer factor therapy and multiple drainage procedures elimniated the skin abscesses. Transfer factor therapy was administered for one year; the patient was asymptomatic 16 months after therapy was discontinued.

Failure of transfer factor therapy in atopic dermatitis

A controlled clinical study was conducted on 6 patients with atopic dermatitis to assess the efficacy of transfer factor. After the code was broken the 3 patients treated with placebo preparation were treated with transfer factor for a further period of 10 weeks. No definite therapeutic effects could be demonstrated. The immunological in vivo and in vitro tests failed to reveal any effects except for a change to positive in the tuberculin skin test in those patients who had previously been skin test negative. The treatment had to be discontinued in one patient due to a suspected allergic reaction against transfer factor.

Transfer factor therapy in a case of pemphigus vegetans associated with chronic mucocutaneous candidiasis

A 19-year-old white male with both pemphigus vegetans and chronic mucocutaneous candidiasis was treated with transfer factor (TF) based on possible common pathophysiologic relationships between these disorders and immune abnormalities. He was incompletely responsive to treatment with prednisolone, methotrexate, and topical micronazole. During 77 weeks of TF therapy, the patient showed gradual but continuous improvement of both diseases characterized by periods of complete remission and occasional mild exacerbations. Administration of other drugs was not necessary. When TF was withheld both diseases flared but regressed after reinstituting TF injections. Thus, TF may be therapeutically beneficial in some patients with the milder forms of pemphigus, and a relationship between cellular immune abnormalities correctable by TF and pemphigus is suggested.

Progressive vaccinia: immunological aspects and transfer factor therapy.

Progressive vaccinia is a rare and serious complication of smallpox vaccination. Depressed immune function can generally be found as an underlying disorder; thus adequate immuno-correction may be expected to be therapeutically effective. Humoral and cell-mediated immunity was repeatedly examined in one case throughout the course of the disease. Results indicated partial deficiency of cell-mediated immunity. No therapeutic effect was achieved by using human antivaccinia immunoglobulin and N-methylisatin beta-thiosemicarbazone. Transfer factor therapy was also attempted. Treatment with a non-specific transfer factor preparation was followed by a transitory clinical improvement. A specific transfer factor preparation given during the last month of life, however, had no therapeutic effect. The patient died on the 145th day after vaccination. Autopsy findings pointed to combined immune deficiency.

Effect of Transfer Factor and Zoster Immunoglobulin in Patients with Varicella-Zoster Infection and Malignancy

Immunotherapy was given to 13 patients suffering from lymphoproliferative diseases complicated by varicella-zoster (VZ) infection. Five patients received transfer factor (TF) only, 6 received TF and zoster immunoglobulin (ZIG), and 2 received ZIG only. ZIG did not seem to alter the course of the infection. Cessation of vesicle formation and initiation of crust formation took place within 1 day after the first injection of TF in 5 patients with a localized zoster. In 4 patients suffering from an early dissemination of VZ infection, cessation of vesicle formation took place within 1 day (1 patient), 2 days (1 patient), 3 days (1 patient) or 4 days (1 patient) after the first injection of TF. An increase in serum interferon was observed in 4 of 9 patients who received TF, while no increase in serum interferon was observed in the control groups. Administration of a high-titer ZIG preparation did not seem to depress the humoral antibody response when combined with TF therapy. Therapy with TF in combination with ZIG seemed to have a beneficial effect in patients with malignancy when administered early in the acute VZ infection.

Chronic Mucocutaneous Candidiasis and Transfer Factor

Chronic mucocutaneous candidiasis (CMCC) is a syndrome characterized by persistent or recurrent Candida infection involving mucous membranes, contiguous and distant skin areas, and nails; it is often associated with an endocrinopathy (endocrine-candidiasis syndrome). There are several forms of this syndrome. Whether these clinical variants and the presence or absence of endocrinopathy represent different forms of a single disease or separate entities is not yet known. Several immunologic defects have been described, but no consistent abnormality has been noted. The author has proposed the hypothesis “immune deviation theory” in the pathogenesis of CMCC.The efficacy of restoration of cellular immunity in therapy of patients with certain chronic infectious or neoplastic diseases is under evaluation in several centers. Theoretically, a substance such as transfer factor (TF) is an ideal candidate for this therapy. TF, a dialyzable substance from blood leukocytes, selectively endows recipients with the cellular immune responses of the leukocyte donors. Moreover, it does not contain intact leukocytes and therefore does not sensitize the recipient to HL-A antigens and cannot induce graft-versus-host disease.Twelve patients with CMCC were treated with TF from randomly selected donors in conjugation with administration of certain antifungal agents such as clotrimazole or amphotericin-B. Mucocutaneous symptoms and signs were predominant at the time that the TF injections were started. Six patients showed remarkable improvement both immunologically and clinically. Patients with CMCC in association with endocrinopathy are unlikely to respond clinically to TF administration although in vitro and/or in vivo changes in cell-mediated immunity may be observed. These results indicate that TF therapy may be beneficial in some cases with CMCC.

Transfer factor treatment of chronic mucocutaneous candidiasis: Requirement for donor reactivity to Candida antigen

Dialyzable transfer factor in conjunction with amphotericin B was used in the treatment of a patient with mucocutaneous candidiasis in a longitudinal controlled study over a 2.5-year period. Amphotericin B treatment alone produced a 3-week remission. Transfer factor from Candida-negative donors could not maintain this remission while transfer factor from donors with strong delayed hypersensitivity to Candida antigen could maintain an amphotericin B-induced remission. Further, this clinical response to transfer factor correlated with the appearance of a positive delayed hypersensitivity skin test to Candida antigen and the production of macrophage migration inhibitory factor (MIF) by the patient's lymphocytes when stimulated by this antigen. This observation supports the hypothesis that successful transfer factor therapy is the result of an antigenspecific conversion from the unreactive to the reactive state and not of nonspecific immunostimulation.

INDICATION OF PRIMARY IMMUNE DEFICIENCY IN FANCONI'S ANEMIA

A girl with various congenital malformations developed pancytopenia and hypoplastic bone marrow at the age of 6 year. A chromosome study of lymphocytes showed numerous breaks, gaps and rearrangements, allowing the diagnosis of Fanconi's anemia. Treatment with corticosteroids and splenectomy did not result in hematologic remission. Repeated immunologic studies showed increasingly deficient T cell function as judged by lymphocyte transformation studies and skin test reactivity, whereas T cell number, T/B cell ratio, immunoglobulins, complement factors and neutrophil function were normal. A sever Pneumocystis carinii pneumonitis developed, but was successfully treated with pentamidine, sulfametoxazole with trimetoprim and transfer factor. Improvement of T cell function followed transfer factor therapy. Combined therapy with corticosteroids and androgens caused partial remission of the hematologic abnormalities. The probability of a primary immune deficiency in the patient is discussed.

Combination immunotherapy in chronic mucocutaneous candidiasis synergism between transfer factor and fetal thymus tissue

A child with chronic mucocutaneous candidiasis and hypothyroidism was found on immunological evaluation to have significant deficits of cell-mediated immunity. Skin anergy and absent lymphocyte transformation to specific antigens as well as failure to produce a lymphokine (macrophage migration inhibitory factor) by antigen-stimulated lymphocytes were observed. Immune responses to mitogens and allogeneic cells were normal. Two courses of combined transfer-factor therapy and amphotericin B did not result in clinical improvement or changes in immunologic function. A 20-week-gestation fetal thymus was transplanted intraperitoneally. Because of persistent deficits in cell-mediated immune function 3 months after thymus transplantation, transfer-factor therapy was reinstituted. Shortly thereafter, lymphocyte proliferative responses to specific antigens developed for the first time. After a partial clinical relapse, a second fetal thymus, 18-weeks gestation, was transplanted concomitant with vigorous transfer-factor therapy. Without further chemotherapy, delayed skin reactivity became positive with clearing of all candidal skin lesions. The success of the combination immunotherapy which resulted in clinical improvement and immunologic reconstitution may have been achieved by the synergistic interaction of transfer factor with the fetal thymus.

Treatment of Bechçet's Syndrome With Transfer Factor

Six patients with Behçet's syndrome were treated with transfer factor (TF) from randomly selected donors. Mucocutaneous symptoms and signs were predominant at the time that TF injections were started. Three patients showed great improvement, one moderate improvement, and one was unresponsive to multiple injections of TF from different donors. One case was uninterpretable because of concomitant administration of high doses of prednisone and chlorambucil and brief treatment with TF. These results indicate that TF therapy may be beneficial in some patients with Behçet's syndrome and that a trial of TF is warranted at least in the absence of severe ocular or neurologic manifestations.

Long-term transfer factor treatment in severe atopic dermatitis.

Transfer factor therapy was applied in three patients with severe atopic dermatitis and given at regular intervals for 1 1/2 years. Clinically, slight improvements were seen, attacks of impetigo ceased and admissions to hospital were not necessary. However, IgE concentrations in serum remained constantly high in all cases and the absolute number of T and B lymphocytes was continuously subnormal despite treatment. The in vitro cellular reactivity to PPD as assayed by a leucocyte migration test was not significantly altered in the patients, although a slight increase was found early on in the therapy. Finally, a serum factor inhibiting leucocyte migration and appearing simultaneously with attacks of impetigo disappeared during treatment. In conclusion, no convincing effect of transfer factor therapy was encountered in immune parameters and no major alterations were found in the status of the patients' atopic dermatitis.

Immunotherapy of Disseminated Renal Cell Carcinoma with Transfer Factor

Ten patients with disseminated renal cell carcinoma have been treated with transfer factor as an immunostimulant. In 5 patients with metastatic disease evident at the time of initial diagnosis treatment involved removal of the primary tumor followed by transfer factor therapy. Of these patients 3 had a temporary stabilization of metastatic disease. Three patients with recurrent metastatic disease after previous nephrectomy were treated, 2 of whom showed a temporary stabilization of metastatic disease. There were 2 additional patients without clinically evident metastases but at a high risk for recurrent disease who were treated and remain free of disease. We used 5 immunologic parameters to evaluate the clinical effects of transfer factor. No objective clinical regression was noted in any patient treated with measurable disease.

Discussion paper: tumor-specific transfer factor therapy in osteogenic sarcoma: a two-year study.

Discussion paper: tumor-specific transfer factor therapy in osteogenic sarcoma: a two-year study.

Transfer factor therapy in patients with cancer.

The objective of this study was to utilize transfer factor to stimulate cell-mediated immunity to specific tumor antigens in cancer patients. Thirty-five selected patients with advanced recurrent cancer, who were not suitable for further conventional therapy, were treated with transfer factor. Transfer factor was prepared from cohabitants of the patients and administered at 2-week intervals. This immunotherapeutic approach produced a clinical effect in 13 patients in terms of regression of tumor (1), arrest of metastatic disease (14), or pain relief (14). Conversion of dermal reactivity to specific tumor antigens was observed during periods of clinical improvement. Despite continued immunotherapy, the duration of clinical improvement was short (2 weeks to 12 months). Seven of the 11 patients not responding to therapy exhibited serum blocking of lymphocyte responsiveness. In 11 patients there is insufficient data to evaluate the clinical effectiveness of this therapy. The results suggest that transfer factor can stimulate specific cell-mediated immunity in cancer patients and produce a clinical effect on tumor under certain circumstances.

Transfer factor therapy in patients with subacute sclerosing panencephalitis.

Thirteen patients with subacute sclerosing panencephalitis (S.S.P.E.) at different stages of the disease were admitted for transfer factor treatment. The transfer factor was prepared from non-selected blood bank donors. The activity of the transfer factor was tested in patients with diseases other than S.S.P.E. and was found to be either clinically or immunologically active. Regardless of the number of transfer factor units applied a significant influence on the course of the disease was not apparant. The observed intermittant improvement of 3 patients was considered as spontaneous remission which is known to occur occasionally in S.S.P.E. The humoral and cellular immune response before and after transfer factor therapy did not reveal significant changes which could be correlated with transfer factor therapy.

Transfer factor: Potential for therapy of malignant diseases.

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.