Joseph M. Hill

Improvement in delayed hypersensitivity in Hodgkin's disease with transfer factor: Lymphapheresis and cellular immune reactions of normal donors

Passive transfer of delayed hypersensitivity was achieved, with normal transfer factor, in patients with Hodgkins disease in remission. The cellular immune responses of the recipients improved. It is suggested that, in addition to specific effect the transfer factor (or factors) has a nonspecific effect causing improvement in the state of delayed hypersensitivity of the recipient in general. The average number of E‐rosette T lymphocytes was 46.3% after the transfer factor treatment in Hodgkins disease. The control patients with Hodgkins disease, not receiving transfer factor, had a value of 37.8%. Removal of 4.9 × 109 to 1.08 × 1010 lymphocytes did not diminish the delayed hypersensitivity of the donor. Side effects attributable to transfer factor were not seen.

Transfer factor in the treatment of herpes simplex types 1 and 2.

Transfer factor potentiates cellular immunity and induces interferon. It was because of these properties that transfer factor was tried in 17 patients with recurrent herpes simplex types 1 and 2. Transfer factor was administered in doses ranging from 5 to 10 U/m2 i. m. The interval between injections varied from 1 week to 3 months. 16 patients could be evaluated clinically in whom the recurrence rate decreased from 10.7 +/- 6.1 to 2.1 +/- 2.5 (mean SD). The reduction was statistically significant. 8 patients were completely free of disease while the other 8 had reduced number of episodes during the period of observation, 7 patients had abnormal T cell function as reflected by the low number of T cells or low lymphocyte transformation. Statistically significant improvement in the T cell function was observed. Delayed hypersensitivity skin test reactions also improved significantly.

Treatment of Acute Leukemia with L-Asparaginase

The Wadley Institutes of Molecular Medicine are now in the third year of clinical investigation and treatment with the first known enzyme capable of depriving tumor cells of their vital nutrition, asparagine.

Isolation and characterization of immunopeptide from dialyzable leukocyte extract

Abstract The dialyzable leukocyte extract was fractionated using high-pressure liquid chromatography through an anion exchange column (preparative). Twenty-one fractions were obtained. Fraction 1, which gave maximum enhancement of E rosettes, was further purified by thin-layer chromatography on silica gel plates. Five ninhydrin-positive bands were seen. The area under each band was scraped from the plates and eluted. The fastest moving component was labeled S1 and the slowest moving S5. Fraction S3 had given maximum enhancement of E rosettes and was designated as immunopeptide. The immunopeptide was further characterized. It contained protein, ribose, and hexose. The molecular weight was determined to be 1870 by sedimentation equilibrium method. It contained 15 amino acid residues. The immunopeptide enhanced E-rosette formation in vivo when given in doses of 5 units/m 2 , to four individuals with low E rosettes.

Suppression of Lymphocyte Blastogenesis in Man Following cis-Platinous Diamminodichloride Administration

Summary The lymphocyte blastogenic response to PHA was studied in patients receiving cis-platinous diamminodichloride for various tumors. This compound produced significant inhibition of blastogenesis (p < .01) in doses ranging from 1 to 4 mg/kg body weight given in different schedules. The inhibition lasted from 18 to 72 hr. A single dose administration produced higher degree of inhibition than divided doses. We thank Mr. Harry Clifford for his technical assistance in carrying out lymphocyte blastogenesis procedure.

Regression of malignant melanoma in a dog by local injections of a partially purified preparation containing human alpha-lymphotoxin.

Abstract Partially purified lymphotoxin preparation containing α-lymphotoxin was investigated for antitumor effect. A 12-year-old male dog weighing 14 kg developed malignant melanoma in the mouth. The tumor measured 4.5 × 4.0 cm. α-Lymphotoxin-containing preparation obtained from human lymphocytes was injected into the tumor at 2– to 5-day intervals. The doses varied from 600 to 2100 units of lymphotoxin activity per injection. A total of 13,200 units of lymphotoxin activity was given over the 30-day period of treatment. The tumor size decreased by 30% during the first 3 days, accompanied by necrosis in the center, and disappeared completely by the 20th day. The remission lasted for 6 months. No untoward effects were seen except for an increase in serum alkaline phosphatase. A repeat biopsy from the tumor site was done 12 days after the completion of treatment which showed fibrosis and lymphocytic infiltration, but no tumor cells. It was suggested that partially purified human α-lymphotoxin preparation possessed antitumor effect across the species barrier. Since the preparation was crude, it is possible that activities other than lymphotoxin were responsible for the antitumor effect. This question can only be resolved when large quantities of pure preparations of lymphotoxin become available.

CLINICAL TRIALS WITH TRANSFER FACTOR

Publisher Summary This chapter presents results of experiments conducted to study clinical trials with transfer factor (TF). The report states that lymphocytes were obtained from healthy donors and contacts of patients utilizing continuous flow centrifuge. Transfer factor was prepared by two techniques: (a) conventional method which utilized dialysis membrane; and (b) Amicon, thin channel system. The report also describe that in view of the transfer factor failure in four melanoma patients, a combined immunotherapeutic approach was taken in two patients with malignant melanoma. Transfer factor was used to enhance the immune responses of the patient followed by local injection of BCG. The results of experiments revealed that dialyzable transfer factor give observable responses in some of the active malignant diseases, alone and in conjunction with other immunotherapeutic approaches. The E-rosette test especially the scoring method, if low, was useful in assessing the need and evaluating the effectiveness of transfer factor treatment.

CIS-Platinum Diamminodichloride in the Treatment of Squamous Cell Carcinoma and Other Malignant Diseases

Two Hundred Nineteen (219) patients with various malignant diseases have been treated with cis-platinum diamminodichloride (PDD) during the last 4 years at the Wadley Research Institute. Early animal trials were done by Rosenberg (1)(5) et al. and Speer and Ridgway (11). Clinical usefulness of PDD has been shown by Hill (10) et al.,Talley (6),Welsch (7),(9) and Higby (13). Commonly employed dosage of PDD was 1/2 mg. to 2.5 mg/kg. Schedules have varied from 1/2 mg/kg. b.i.d. to the maximum single dose of 2.5 mg/kg. Total course doses varied ordinarily from 2 to 4 mg/kg. with an interval between courses of at least one month. Treatment was pursued until limiting toxicity or complete remission was observed. The toxic reaction causing the most concern is dose related renal tubular damage. BUN, creatinine, uric acid and creatinine clearance were closely followed. Urine creatinine clearance less than 50 cc/min.disqualified the patient from PDD treatment. Side effects related to hypersensitivity were only seen in one case recently reported by Dr.Khan (15) et al. PDD was used alone and in combination with other drugs such as amethopterin (AME) cyclophosphamide, thioguanine (Protocol designated as PACT) or followed by 5 FU, cyclophosphamide, vincristine, AME, given over 5 days or bleomycin, vincristine or vinblastine.

THE ROLE OF TRANSFER FACTOR IN THE TREATMENT OF LYMPHOMA CUTIS IN WISKOTT-ALDRICH SYNDROME

Publisher Summary This chapter highlights results of experiments conducted to study the role of transfer factor (TF) in the treatment of lymphoma cutis in Wiskott–Aldrich syndrome. The chapter also discusses a case report where a 17-year-old white male with Wiskott–Aldrich syndrome developed lymphoma cutis after receiving transfer factor for 20 months. The patient was given large doses of transfer factor. It was suggested in the report that delayed hyper sensitivity to five different antigens could not be transferred passively with dialyzable transfer factor to the patient with Wiskott–Aldrich syndrome and lymphoma cutis. The patient was unresponsive to dinitrochlorobenzene (DNCB) sensitization. It was observed that the reaction to DNCB became more intense following a second dose of transfer factor which was prepared from an unsensitized (DNCB) donor. The results revealed that the patient had a wart on his right hand. The warts are associated with papova group of viruses. It was noted that his wart disappeared following DNCB sensitization.

FRACTIONATION OF TRANSFER FACTOR WITH HIGH PRESSURE LIQUID CHROMATOGRAPHY AND E-ROSETTE ENHANCING ACTIVITY OF VARIOUS FRACTIONS

Publisher Summary This chapter describes fractionation of transfer factor with high pressure liquid chromatography and e-rosette enhancing activity of various fractions. Dialyzable transfer factor is prepared from leukocytes which are comprised of all the subpopulations of lymphocytes and a various percentage of granulocytes and monocytes. Six fractions were collected. Transfer factor has been shown to enhance the E-rosette (ER) formation by lymphocytes obtained from patients with immunodeficiency and malignant diseases. It did not increase ER in normal lymphocytes, significantly. The ER enhancing activity of each fraction was investigated. The details of the techniques for determining percentage of ER forming cells and the ER scores have been described. Plasma was not used in the ER test to avoid the possibility of adding other ER enhancing factors. The lymphocytes utilized for this purpose were obtained from patients with immunodeficiency or malignant disease that had low ER. It appears that there are different polypeptides present in the transfer factor.