Arch Otolaryngol 1975 Nov;101(11):664-6Transfer 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, UI: 76087317
Arch Geschwulstforsch 1981;51(4):284-93The present status of immunodiagnosis and immunotherapy of cancer
A number of immunodiagnostic procedures in cancer is clinically important in the sense that the tests may confirm the results of other cancer diagnostic investigations. However, each one of the tests has its own area of application. Immunodiagnostic tests are used for the detection of relapse or metastases as well as for the histological verification of the tumor. A mass screening for tumors in the population and most probably the early tumor diagnosis by immunological means is impossible due to biological variables among the tumor bearers and to technical difficulties. Immunotherapy of tumors is still at an experimental stage. Although immunization is possible to animal tumors convincing data on similar effects in the human tumor system do not exist as yet. This conclusion is based on immunization experiments with adjuvants as well as with tumor preparations, transfer factor, thymosin, or immune RNA. The fact that tumor cytotoxic and tumor cytostatic immunological mechanisms do occur even in the human tumor system is a stimulus for future approaches.
Ann Thorac Surg 1984 Aug;38(2):140-5 (ISSN: 0003-4975)Transfer factor in the treatment of carcinoma of the lung
Kirsh MM; Orringer MB; McAuliffe S; Schork MA; Katz B; Silva J
From 1976 to 1982, 63 patients with carcinoma of the lung underwent curative pulmonary resection, mediastinal lymph node dissection, and postoperative mediastinal irradiation when indicated. After operation, the patients were randomized by cell type and stage of disease into two groups. Beginning 1 month postoperatively, Group 1 patients (N = 28) received 1 ml of transfer factor that had been extracted from the blood of normal individuals. Subsequent doses were administered at 3-month intervals. Group 2 patients (N = 35) served as controls. There were no significant differences between the two groups with respect to age, sex, extent of resection, histological cell type, or stage of disease. Twenty of the 28 treated patients were alive and free from disease from 7 to 77 months after treatment, whereas 17 of the 35 control patients were free from disease. The 1-year survival for Group 1 was 84% and for Group 2, 81%. The 2-year survival was 78% for Group 1 and 46% for Group 2 (p = 0.045). The survival rates by stage of disease were as follows: Stage I, 15 out of 17 or 88% in Group 1 and 15 out of 23 or 65% in Group 2 (p = 0.097); Stages II and III, 5 out of 11 or 45% in Group 1 and 3 out of 12 or 25% in Group 2 (p = 0.304). The results of the study suggest that the administration of transfer factor to patients who have undergone pulmonary resection for carcinoma of the lung can have a significant impact on the prolongation of life.
Jpn J Surg 1984 Nov;14(6):452-8Randomized controlled trial of transfer factor immunochemotherapy as an adjunct to surgical treatment for primary adenocarcinoma of the lung
Fujisawa T, Yamaguchi Y, Kimura H, Arita M, Shiba M, Baba M.
A total of 102 patients were studied in a randomized controlled trail to evaluate the clinical effect of transfer factor (TF) for primary resected adenocarcinoma of the lung. The TF and Control groups consisted of 50 and 52 randomly chosen patients, respectively. However, 6 and 5 patients were excluded from both groups for various reasons, therefore the total of cases eligible for evaluation were 44 and 47 in the TF and Control groups, respectively. The clinical features of both groups were similar. The survival of the TF group was significantly better than that of Controls in Stage I cases (p less than 0.05), however, there was no significant difference in patients in Stages II, III and IV. Significant differences were found between the TF and Control groups in curative resection cases (p less than 0.05), however, no significant difference was seen in either the relatively curative resection or noncurative resection groups. TF seems to inhibit postoperative recurrence and appears to be an effective postoperative adjuvant immunotherapeutic for primary resected adenocarcinoma of the lung, especially at the relatively early stages.
Cancer 1996 Nov 1;78(9):1892-8Postoperative immunostimulation after complete resection improves survival of patients with stage I non-small cell lung carcinoma
FujisawaT,YamaguchiY.Department of Surgery, Chiba University School of Medicine, Japan.
BACKGROUND: approximately 40% of primary lung carcinoma patients who die within 1 month after a complete resection have residual tumor in regional or distant organs, emphasizing the importance of postoperative adjuvant therapy. In this study, the effectiveness of transfer factor (TF) and nocardia rubra-cell wall skeleton (N-CWS) as adjuvant therapy for patients with primary, completely resected non-small cell carcinoma of the lung was evaluated in a randomized controlled trial METHODS: A total of 82 patients with Stage I disease who had a complete resection were allocated randomly into 2 groups: TF + N-CWS (n = 41) or control (surgery only) (n = 41). RESULTS: The distributions of age, sex, histology, differentiation, T classification, tumor size, visceral pleural invasion, and the site of origin, were similar in the two groups. The 5- and 10-year disease specific survival rates in the TF + N-CWS group were 85% and 85%, respectively, and those in the control group were 72% and 64%, respectively. There was a statistically significant difference between the two groups (P = 0.041). When the survival was analyzed according to clinical characteristics, significant differences were observed in patients with no visceral pleural invasion or with T1 disease. The frequency of distant metastasis was significantly less in the TF + N-CWS group than in the control group. CONCLUSIONS: These results indicate that TF + N-CWS is beneficial as adjuvant therapy after surgical treatment of Stage I non-small cell carcinoma of the lung.
Biotherapy 1996;9(1-3):117-21Transfer factor as an adjuvant to non-small cell lung cancer (NSCLC) therapy
Pilotti V, Mastrorilli M, Pizza G, De Vinci C, Busutti L, Palareti A, Gozzetti G, Cavallari A.
Istituto di Clinica Chirurgica II, S. Orsola-Malpighi, Bologna, Italy.
The rationale for using transfer factor (TF) in lung cancer patients is that the possibility of improving their cell-mediated immunity to tumour associated antigens (TAA) may improve their survival. From Jan 1984 to Jan 1995, 99 non-small cell lung cancer (NSCLC) resected patients were monthly treated with TF, extracted from the lymphocytes of blood bank donors. In the same period, 257 NSCLC resected patients were considered as non-treated controls. The survival rates of the TF treated group appear significantly improved both for patients in stages 3a and 3b, and patients with histological subtype "large cell carcinoma" (P < 0.02). Survival of TF treated patients is also significantly higher (P < 0.02) for patients with lymph node involvement (N2 disease). The results of this study suggest that the administration of TF to NSCLC resected patients may improve survival.
Ann Thorac Surg 1992 Mar;53(3):391-6Adjuvant treatment using transfer factor for bronchogenic carcinoma: long-term follow-up
Whyte RI, Schork MA, Sloan H, Orringer MB, Kirsh MM.
Section of Thoracic Surgery, University of Michigan, Ann Arbor.
Transfer factor, a dialyzable lymphocyte extract that may act as an immune stimulator by transferring antigen-specific immunity between genetically dissimilar individuals, was administered in a prospective, randomized study to patients with non-small cell bronchogenic carcinoma. Between 1976 and 1982, 63 patients who underwent pulmonary resection, mediastinal lymph node dissection, and, when indicated by the presence of mediastinal lymph node involvement, mediastinal irradiation were randomized into two groups. Group 1 (n = 28) received 1 mL of pooled transfer factor at 3-month intervals after operation; group 2 (n = 35 ) served as controls and received saline solution. There were no statistically significant differences between the two groups with respect to age, sex, tumor histology, stage of disease, or extent of resection. One patient was lost to follow-up at 96 months; follow-up was complete in all others through July 1990. In patients receiving transfer factor, the 2-, 5-, and 10-year survival rates were 82%, 64%, and 43% respectively, whereas in controls they were 63%, 43%, and 23%. Survival in patients receiving transfer factor was consistently better than in those receiving placebo. Furthermore, survival in patients receiving transfer factor was greater at all stages of disease for both adenocarcinoma and squamous cell carcinoma. Although these long-term results were not statistically significant using survival analysis with covariates (p = 0.08), they confirm our previously reported short-term findings suggesting that administration of transfer factor, either through nonspecific immune stimulation, enhancement of cell-mediated immunity, or an as yet undefined mechanism, can improve survival in patients with bronchogenic carcinoma.
J Biol Response Mod 1987 Feb;6(1):1-19 (ISSN: 0732-6580)Observations on the combined systemic administration of mixed bacterial vaccine, bacillus Calmette-Guerin, transfer factor and lymphoblastoid lymphocytes to patients with cancer, 1974-1985
Herein are reported the results of treating 139 cancer patients with combined immunomodulation that consisted of bacillus Calmette-Guerin, transfer factor, and mixed bacterial vaccine. In addition 28 patients were given infusions of lymphoblastoid lymphocytes. Patients were admitted to this treatment program who either had failed to respond to other modalities, had elected to add immunomodulation to usual therapy, or had refused chemotherapy and/or radiation therapy. The results suggested that combined immunomodulation therapy is well tolerated and safe and that this approach on a prima facie basis had a salutary effect on the courses of a number of the patients treated. The results also illustrate alternative pathways that can be taken by patients and physicians who are not comfortable with protocolized double-blind methods of approaching patients with poor prognosis cancer.
Br J Haematol 1993 Jul;84(3):423-7Effect of transfer factor on myelosuppression and related morbidity induced by chemotherapy in acute leukaemias
Fernandez O, Diaz N, Morales E, Toledo J, Hernandez E, Rojas S, Madriz X, Lopez Saura P.
Hospital Universitario Dr. Carlos J. Finlay, Marianao, Cuba.
The aim of this study is to determine the safety and efficacy of Transfer Factor (TF) in accelerating the haematopoietic recovery in patients with acute leukaemias (AL), following intensive therapy to induce remission of the disease. Twenty-two patients with different types of AL (16 AML, three BC-CML and three ALL) were studied. The patients were divided in two groups. Group 1 (eight AML, two BC-CML and one ALL) received, after myelosuppression induced by chemotherapy, TF (1 unit daily, subcutaneous) until leucocyte count was > 2.5 x 10(9)/l and platelet count > 80 x 10(9)/l. Group 2 was considered the control group and did not receive TF. Treatment with TF accelerated the recovery of neutrophils, leucocytes, platelets (P < 0.001) and haemoglobin (P < 0.01). As a logical consequence, incidence and severity of infection and haemorrhage were lesser in the TF group than in the control group. There was no evidence that TF accelerated the re-growth of leukaemic cells. It seems that TF is safe in AL, accelerating haematopoietic recovery. However, it should be used with caution until results of additional trials become available.
Microbiol Immunol 1978;22(11):701-10In vitro assay for responsiveness of lymphocytes to transfer factor by a new leukocyte migration inhibitory test
Miyagawa Y, Kawasaki A, Komiyama A, Akabane T.
Transfer factor (TF) causes nonimmune lymphocytes to produce leukocyte migration inhibitory factor (LMIF) in the presence of purified protein derivative (PPD). The activity of TF was measured by leukocyte migration inhibitory test (LMIT). The LMIT was a modification of the conventional agarose droplet method. To express the activity of LMIF quantitatively and simply, LMIF titer was introduced. The LMIF titer was obtained from the combination of two factors, LMIF dilution and cell migration diameter, and therefore this made the LMIT much more sensitive as compared to the conventional LMIT. The responsiveness of lymphocytes from acute lymphoblastic leukemia (ALL) and from cell-mediated immunodeficiency in children to TF was assayed by LMIT. In ALL, the lymphocyte responsiveness was poor in relapse but improved with remission. The responsiveness was remarkably well in 3 patients with cell-mediated immunodeficiency. This method appears useful for the in vitro evaluation of responsiveness of lymphocytes to TF.
Med Pediatr Oncol 1979;6(4):295-301A study of transfer factor for opportunistic infections in cancer patients
Ketchel SJ, Rodriguez V, Stone A, Gutterman JU.
Although supportive care during therapy of patients with malignancies has improved, infection remains the major cause of death in these patients. The problem of "opportunistic" infections is becoming more apparent as better antibiotics are found. The control of these infections depends in part on mechanisms of cell-mediated immunity. It has been demonstrated that delayed-type hypersensitivity can be transferred from one person to another. Therefore, we used transfer factor in the treatment of 15 patients, most with leukemia, who had fungal, viral, or mycobacterial infections that were not responding to conventional therapy. Seven of ten evaluable patients had therapeutic control of their infections while receiving transfer factor. Transfer factor appears to have contributed to these clinical improvements and is a modality of treatment that deserves further investigation.
Scand J Infect Dis 1978;10(1):21-7Effect of transfer factor and zoster immunoglobulin in patients with varicella-zoster infection and malignancy
Winsnes R, Froland SS, Degre MI.
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.
Ann Allergy 1982 Dec;49(6):326-9Transfer factor
Massicot JG, Goldstein RA.
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.
Summer;3(4):463-9Transfer factor in prevention of Burkitt's lymphoma relapses
J Exp Pathol 1987 Nkrumah FK, Pizza G, Neequaye J, Viza D, De Vinci C, Levine PH.
Burkitt Tumour Project, Univ. of Ghana Medical Sch. Accra.
Twenty-two African children with endemic Burkitt's lymphoma entered a study to evaluate the possible efficacy of a transfer factor (TF) with specific activity against Eptein-Barr virus in preventing disease relapses. Five of eleven patients have so far relapsed in the non TF-treated group as against two of eleven in the TF-treated group. The patterns of relapse and observable increased disease free remission duration in the TF-treated group strongly suggest a beneficial effect particularly in the prevention of late relapses. A larger series of patients treated with this specific TF are needed to confirm these observations in endemic Burkitt's lymphoma.
Wien Klin Wochenschr 1983 Oct 28;95(20):738-42 [Article in German]Transfer factor as adjuvant immunotherapy in invasive cervix cancer. Report of a double-blind study
Wagner G, Gitsch E, Havelec L, Knapp W, Rainer H, Selander S.
From 1977 to 1982 a prospective randomized double-blind study comparing transfer-factor (TF) versus placebo was conducted in invasive cervical cancer patients after radical surgery and irradiation. The husbands of the cancer patients were selected as leukocyte donors for TF preparations. 60 patients entered the study; 28 patients received placebo and 32 patients received TF. The comparability of both collectives was excellent concerning age and tumor stage. One patient treated with TF died intercurrently. The rate of recurrence of cancer was 5 in the 31 TF-treated patients and 11 in the 28 patients receiving placebo, which was significantly different (p less than 0,05). This difference was even greater when only patients treated for at least 3 months were compared (3 recurrences in the TF-group and 11 recurrences in the placebo-group). Further aspects of this clear clinical results are discussed.
Biotherapy 1996;9(1-3):123-32A preliminary report on the use of transfer factor for treating stage D3 hormone-unresponsive metastatic prostate cancer
Pizza G, De Vinci C, Cuzzocrea D, Menniti D, Aiello E, Maver P, Corrado G, Romagnoli P, Dragoni E, LoConte G, Riolo U, Palareti A, Zucchelli P, Fornarola V, Viza D.
Immunodiagnosis and Immunotherapy Unit, S. Orsola-Malpighi Hospital, Bologna, Italy.
As conventional treatments are unsuccessful, the survival rate of stage D3 prostate cancer patients is poor. Reports have suggested the existence of humoral and cell-mediated immunity (CMI) against prostate cancer tumour-associated antigens (TAA). These observations prompted us to treat stage D3 prostate cancer patients with an in vitro produced transfer factor (TF) able to transfer, in vitro and in vivo, CMI against bladder and prostate TAA. Fifty patients entered this study and received one intramuscular injection of 2-5 units of specific TF monthly. Follow-up, ranging from 1 to 9 years, showed that complete remission was achieved in 2 patients, partial remission in 6, and no progression of metastatic disease in 14. The median survival was 126 weeks, higher than the survival rates reported in the literature for patients of the same stage.
Biotherapy 1996;9(1-3):109-15Transfer factor with anti-EBV activity as an adjuvant therapy for nasopharyngeal carcinoma: a pilot study
Prasad U, bin Jalaludin MA, Rajadurai P, Pizza G, De Vinci C, Viza D, Levine PH.
University of Malaya, Kuala Lumpur, Malaysia.
Overall survival of nasopharyngeal carcinoma (NPC) at UICC stage IV still remains unsatisfactory even with combination chemotherapy (CT) and radio-therapy (RT). In view of the association of reactivation of Epstein-Barr virus (EBV) with the development and recurrence of NPC, immunotherapy in the form of transfer factor (TF) with specific activity against EBV (TF-B1) was suggested as an adjuvant to a combination of CT and RT in order to improve survival. In the present study, 6 UICC stage IV patients received TF-B1 and another 6 patients matched for disease stage were given TF prepared from peripheral blood leucocytes (TF-PBL). Results were compared with another 18 patients matched by age, sex, and stage of disease who received standard therapy without TF during the same period (C group). After a median follow up of 47.5 months, the survival for the TF-B1 group was found to be significantly better (P = < 0.05) than the PBL and C group. While the 8 patients with distant metastasis (DM), not treated with TF-B1 (6 in the control and 2 in the PBL group), died due to progressive disease (average survival being 14.3 months), both patients with DM in the TF-B1 group had complete remission: one died of tuberculosis after surviving for 3.5 years and another is still alive, disease free, after 4.2 years. Although the series involved a small number of cases, the apparent effect of adjuvant immunotherapy in the form of TF with anti-EBV activity is of considerable interest.
Panminerva Med 1995 Dec;37(4):186-9Serial in vitro transfer of hypersensitivity to cancer antigens by sensitised lymphocytes
Fazio M, Carnevale-Schianca F, Sabidussi A.
Chair of Medical Oncology, University of Turin, Italy.
An account is given of the experimental serial in vitro transfer of antigen-specific delayed hypersensitivity to peripheral leukocytes, using antigen-specific Transfer factor solely as the initial source. Transfer was assessed with the leukocyte migration, lymphocyte locomotion and leukocyte adherence inhibition tests. The positive test results observed in all the experiments suggest that Transfer factor does not act as such, but triggers a reaction that expands the effect of hypersensitivity.