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Biomedical subjects

L E Spitler

Publications and source records attributed to L E Spitler.

At least 37 records · Page 2Linked to original sources
PubMed1987

Toxicity and immunogenicity of monoclonal antimelanoma antibody-ricin A chain immunotoxin in rats.

This study was performed to assess the subacute toxicity and immunogenicity in rats of XOMAZYME-MEL, an antimelanoma monoclonal antibody-ricin A chain immunotoxin. Female Sprague-Dawley rats received 14 consecutive daily i.v. injections of XOMAZYME-MEL at doses of 5 mg/kg/day, 1 mg/kg/day, or normal saline. Animals from each dose group were sacrificed on days 8, 15, and 22. The low dose of immunotoxin was well tolerated and produced only minimal signs of toxicity. Side effects in animals receiving the high dose of immunotoxin consisted of transient weight loss, peripheral edema, leukocytosis, hypoalbuminemia, and mildly elevated liver function tests. Histological findings in these animals included cytoplasmic vacuolization of hepatocytes, focal myocardial and skeletal muscle degeneration, and renal deposits of proteinaceous casts. The administration of immunotoxin resulted in the appearance of anti-mouse and antiricin A chain immunoglobulin binding activity in the sera of treated animals. This study documents the systemic effect of the multiple-dose administration of a ricin A chain immunotoxin in rats.

Animals↗
PubMed1987

Humoral immune response to a ricin A chain immunotoxin in patients with metastatic melanoma.

Immunotoxins, hybrid molecules consisting of a monoclonal antibody linked to a polypeptide toxin have shown anti-tumor activity in both animal models and early clinical trials. However, their potential value in the treatment of human cancer may be limited by the development of host antibodies against the conjugate. Such antibodies could potentially alter immunotoxin pharmacokinetics and pharmacodynamics as well as precipitate serum sickness or anaphylaxis. Using a radioimmunoassay we have measured serial anti-ricin A chain (anti-RTA) and anti-murine immunoglobulin (anti-MIG) titers in 22 patients who received the anti-melanoma immunotoxin XomaZymeR-Mel. Significant titers of anti-RTA and/or anti-MIG were detected in 17 of 21 evaluable patients. Of the four patients not developing antibodies, two were likely immunosuppressed secondary to dexamethasone, and CCNU and dexamethasone respectively. Both patients who received immunotoxin at a time when they had detectable anti-immunotoxin antibodies experienced infusion reactions consistent with immune mediated allergic responses. There was a decrease in peak immunotoxin level in the one patient who had serum immunotoxin levels measured at a time when anti-RTA was present. Strategies to suppress the human immune response to immunotoxins are required before repetitive courses of immunotoxin of this design may be administered.

Adult↗
PubMed1987

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↗
PubMed1986

Immunotoxin therapy of malignant melanoma.

Current standard therapies for metastatic malignant melanoma are poor, and surgical excision of disease remains the cornerstone of melanoma management. Unmodified monoclonal antibodies have been used therapeutically in this, and other, malignancies, but results have been disappointing. This has led to attempts to improve the efficacy of monoclonal antibodies by using them to target therapeutic modalities to tumors. These therapeutic modalities include chemotherapeutic, radiotherapeutic and cytotoxic agents. An example of the latter is ricin A-chain, which is so potent that it has been reported that one molecule of it entering the cytosol is sufficient to cause cell death. Preclinical studies support the potential of immunotoxins as effective therapy for malignancy. A phase I-II trial of immunotoxin therapy of malignant melanoma has been completed and a trial to determine clinical efficacy has been implemented.

Antibodies, Monoclonal↗
PubMed1986

Improved immune-specificity in monoclonal radioimmunoimaging using dual radionuclide color functional maps.

Diagnostic radioimmunoimaging is potentially limited by tissue localization of radiolabeled antibody products through mechanisms other than antigen binding. Comparing the distributions of reactive and nonreactive products can distinguish tracer in targeted and nontargeted tissues. To achieve this in a single imaging procedure, dual photopeak scintigraphy was performed using 111In and 67Ga products. Melanoma-bearing athymic mice were coadministered intravenously subtype-matched 111In melanoma-reactive and 67Ga melanoma-nonreactive murine monoclonal antibodies. Paired images from 245 and 93 keV windows were processed with a unique dual parameter color display program. The display algorithm expresses pixel counts from paired photo-peak images in polar coordinates and color-encodes angle as hue and magnitude as intensity. The color functional maps permitted ready distinction of immune from nonimmune uptake. Compared with single tracer imaging methods, this technique better depicts antigen distribution.

Animals↗
PubMed1986

Phase 1 immunolymphoscintigraphy with an In-111-labeled antimelanoma monoclonal antibody.

A phase 1 study was conducted using a monoclonal antimelanoma antibody-DTPA conjugate labeled with indium-111, for immunolymphoscintigraphy in patients with metastatic melanoma. The imaging agent, labeled with 1 mCi (37 MBq) In-111, was administered as an interstitial interdigital injection to six patients scheduled to undergo lymph node dissection for suspected metastatic malignant melanoma. No adverse effects were observed in any of the patients either during or after the infusion as determined by clinical and laboratory parameters. Antibodies to the murine immunoglobulin were produced in some patients. Regional lymph nodes were visualized whether tumor-bearing or not, and light microscopic autoradiography showed In-111 activity associated with histiocytes. One of two patients harboring both tumor-bearing and tumor-free lymph nodes exhibited preferential localization in tumor-bearing nodes. The authors conclude that this study demonstrates safety of the radiopharmaceutical and that further study is needed to improve its usefulness for diagnosis of lymph node metastases.

Adult↗
PubMed1984

Purification of monoclonal antibodies from mouse ascites eliminates contaminating infectious mouse type C viruses and nucleic acids.

We examined the fate of infectious mouse type C viruses (MuLV) and nucleic acids during the purification of monoclonal antibodies (MoAbs) from mouse ascites. Hybridoma cell lines and their cell fluids can contain infectious ecotropic and xenotropic MuLV whose presence in ascitic fluid may be masked by the presence of anti-viral factors, particularly the anti-xenotropic virus neutralizing factor. They can also contain DNA and RNA. The specific techniques we used for the purification of MoAbs from the ascitic fluid completely eliminated all detectable infectious MuLV, anti-viral factors, and nucleic acids, even when these agents were added in quantities far in excess of those normally expected. Viral proteins, potentially contaminating the MoAb preparations, were also substantially reduced by our procedures. Because infectious MuLV or nucleic acids may have adverse effects on human subjects, attention should be given to each MoAb purification process to insure their effective removal.

Animals↗
PubMed1983

Lymphocytotoxic antibody in multiple sclerosis: activity against T cell subsets and correlation with disease activity.

Lymphocytotoxic activity has been found by previous investigators in multiple sclerosis (MS) sera. We confirmed the presence of this activity in MS sera using techniques designed to eliminate possible sources of erroneous conclusion not considered in previous studies. We further characterized this activity and found it to be non-dialysable and complement dependent, and, therefore, presumably to be an antibody. This lymphocytotoxic antibody (LCA) is found in those patients with active or progressive disease, and appears to be preferentially directed against the suppressor subset of T cells, as defined by monoclonal antibodies. The LCA may play a role in the pathogenesis of acute exacerbation of MS.

Antibodies, Monoclonal↗
PubMed1981

Serum copper and zinc levels in melanoma patients.

Serum copper levels (SCL) and serum zinc levels (SZL) were evaluated in malignant melanoma patients at various clinical stages. Copper levels were generally found to be elevated, reflecting the degree and extent of tumor activity. Zinc levels and, hence, SCL:SZL ratios did not reflect tumor activity. SCL appeared to prognosticate disease progression in that all patients whose values never declined below 150 micrograms/100 ml died during the course of the study. However, not all patients who died from tumor metastases displayed persistent elevations of SCL. Patients receiving BCG immunotherapy appeared to have higher SCL than untreated patients.

Adult↗
PubMed1981

Treatment of Behcet's syndrome with levamisole.

The clinical response to levamisole in 11 patients with complete Behcet's syndrome was reviewed. Nine patients responded, 3 completely and 6 partially, with reduction in the number and severity of buccal and genital lesions. In 3 patients each, ocular inflammation and gastrointestinal involvement responded to levamisole, and in 1 patient neurologic status improved. Levamisole was purposely discontinued in 3 patients to assess its true role in disease control. Each patient experienced a flare. Reintroduction of therapy controlled the flare in all cases, although 1 patient subsequently relapsed while continuing therapy. Two patients failed to respond. Side effects necessitated permanent discontinuation of the drug in 2 respondent patients, but in no case did neutropenia or agranulocytosis develop. These preliminary results suggest that levamisole may be useful in the therapy of the various manifestations of Behcet's syndrome and that a controlled prospective study is indicated.

Adolescent↗
PubMed1981

Transfer factor therapy for histoplasmosis in a patient with Hodgkin's disease.

A patient with recurrent chronic histoplasmosis was diagnosed also as having Hodgkin's disease. Studies of cell-mediated immunity (CMI) demonstrated no reaction to histoplasmin by skin test, lymphocyte transformation (LT), or leukocyte inhibition factor (LIF) assay. Clinical and immunologic studies were performed during treatment with 19 doses of dialyzable transfer factor (TF) prepared from a normal donor with strong CMI against histoplasmin. Transfer of CMI to the patient was demonstrated by all three tests. All tests reverted to nonreactive during the period of observation. Repeated doses of dialyzable TF were followed by reconversion of skin tests. The LIF assay was most reactive. Reactivation of histoplasmosis occurred during antimetabolic therapy for Hodgkin's disease; however, the lesions cleared rapidly when TF was added to amphotericin B. Amphotericin B was administered at a dosage of 25 mg three times each week during the entire study.

Adult↗
PubMed1980

Immunologic mechanisms in multiple sclerosis. Exacerbation by type A hepatitis and skin test antigens.

A 29-year-old man with quiescent multiple sclerosis had hemiparesis during the prodrome of serologically confirmed type A hepatitis. After neurological symptoms and acute hepatitis had abated, hemiparesis again developed when skin tests were applied. While he was receiving prednisone, skin test inflammation and neurological signs cleared. One year later, lymphocyte stimulation, which had been noticeably elevated during his exacerbations, returned to low normal. Both hepatitis A and skin test antigens produced immunostimulation that resulted in exacerbation of multiple sclerosis.

Acute Disease↗
PubMed1980

A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma.

We conducted a randomized double-blind trial of levamisole versus placebo as adjuvant therapy for surgical treatment of melanoma. Of 203 patients entered into the study, 104 received levamisole and 99 placebo. The distribution of prognostic variables was similar in both groups, indicating the efficacy of the randomization and the absence of bias. Three end points were analyzed: disease-free interval, time to appearance of visceral metastasis, and survival. There was no statistically significant difference between the groups regarding any of these end points. In patients with Stage I disease, there was a trend in favor of levamisole regarding time to first visceral recurrence and survival (P = 0.07). We conclude that levamisole has no benefit, as compared with placebo, as adjuvant therapy for malignant melanoma.

Adult↗
PubMed1980

Adjuvant immunotherapy with transfer factor in patients with melanoma metastatic to lung.

Nine patients with resectable pulmonary metastases of malignant melanoma were treated with surgery and transfer factor. Twelve months after thoracotomy, all were alive. After a median follow-up of 20 months, only one patient had died. Historic, other-center controls treated with surgery alone had a significantly (p less than 0.025) lower survival rate. Recurrence rates tended to be lower in the transfer factor group, but the differences were not significant. These results suggest that transfer factor may prolong survival in patients with an immunologically responsive malignancy and a small residual tumor burden.

Adolescent↗
PubMed1980

Transfer factor: failure to transfer reactivity in normal human subjects.

Transfer factor was prepared from highly selected normal donors. One lot was made from donors strongly reactive to coccidioidin and negative to Dharmendra antigen in in vivo and in vitro testing. The other lot was made from donors without reactivity to coccidioidin and strongly reactive to Dharmendra. Aliquots of each lot were injected into eight normal recipients. Eight additional normal recipients were given placebo injections. Before and after injection, skin test reactivity and in vitro testing were evaluated by an individual who did not know which preparation the patient received. Changes in immunologic reactivity in subjects receiving transfer factor could not be distinguished from those in subjects receiving placebo. I conclude that transfer factor does not cause enhancement of immunologic reactivity in normal subjects. A well designed, critical study is needed to determine whether or not it does, in fact, cause enhancement of immunologic reactivity in patients with impaired cellular immune reactivity.

Antigens↗
PubMed1980

Nephropathy in the Wiskott-Aldrich syndrome.

Nephropathy was detected in five of 32 patients with the Wiskott-Aldrich syndrome who were participating in a study of transfer factor (TF) therapy. In two patients, nephropathy was present before TF and did not appear changed by TF therapy. One of these patients subsequently developed progressive renal failure requiring dialysis beginning 5 1/2 years after TF therapy. In two patients, decreased renal function appeared very soon after the administration of TF. One patient showed gradually decreasing renal function beginning after two years of TF therapy. An additional patient was identified who died with renal failure without having received TF. The results suggest that renal failure occurs in the Wiskott-Aldrich syndrome more frequently than generally recognized and that administration of TF may precipitate or accelerate the renal disease in patients with this syndrome.

Adolescent↗