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[Hemosorption in serotherapy (serosorption) in experimental acute diphtheric toxemia with the use of affinity sorbents].

In modeling acute diphtheric toxemia in guinea pigs, the authors propose to perform hemosorption using selective sorbents under continuous introduction of antitoxic immune sera into extracorporeal contour in front of sorption column. Combination of hemosorption with serotherapy in the same time interval may be denoted as serosorption. As specific sorbents, affine preparations imasorb A-700 and Imasorb G-700 were used. They selectively eliminate from the blood flow CIC produced by diphtheric toxin (anatoxin) and antitoxic rabbit and horse antibodies. Changes in the titers of the diphtheric toxin (anatoxin) and CIC in blood evidence for efficiency of selective sorbents were confirmed by immunohistochemical analysis of the preparations' granules after hemoperfusion.

Animals↗

The use of antidiphterial serotherapy in Bologna in 1895. A pilot experience.

It was the year 1894 and the international scientific community was experiencing a historic moment. It was around this time that Pasteur, Kock, L efler, Yersin and Behring discovered the microbiological causes of commonly occurring infectious diseases. In Bologna it was decided to eradicate the diphtheria epidemic which had claimed 152 victims, mainly children, the previous year by experimentally adopting specific serotherapy successfully applied in France shortly before. Supported by local government funding and with the aid of some enterprising local doctors, an efficacious serum was soon produced in Bologna. Good clinical results were obtained and production and sale costs were able to be considerably reduced. Little more than a century later, this is an example of applicative research where there is much still to be revealed.

Journal Article↗

[The efficacy of vaccination and serotherapy in tick-borne encephalitis in the Maritime Territory].

The use of different vaccines manufactured in the USSR under the condition of the Far East has revealed that killed vaccines do not produce a protective effect, sufficient for the prophylaxis of tick-borne encephalitis (TBE). This is probably due to the circulation of a highly virulent population of TBE virus at the Territory. This virus population may produce a severe course of infection and aggravate the clinico-epidemiological characteristics of the effectiveness of vaccines. Besides, low levels of specific and nonspecific humoral resistance factors in the residents of the Far East, especially in spring and summer, contribute to this fact. The negative effect of specific serotherapy for persons over 40 years of age has been established.

Adolescent↗

Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas.

Four patients with refractory malignant B cell lymphomas were treated with continuous intravenous (IV) infusions of murine monoclonal antibody (MoAb) 1F5 (anti-CD20) over five to ten days. Dose-dependent levels of free serum 1F5 were detected in all patients. Two patients had circulating tumor cells and in both cases 90% of malignant cells were eliminated from the blood stream within four hours of initiation of serotherapy. Antigenic modulation did not occur, and sustained reduction of circulating tumor cells was observed throughout the duration of the infusions. Serial bone marrow aspirations and lymph node biopsies were examined by immunoperoxidase and immunofluorescence techniques to ascertain MoAb penetration into extravascular sites. High doses (100 to 800 mg/m2/d and high serum 1F5 levels (13 to 190 micrograms/mL) were required to coat tumor cells in these compartments in contrast to the low doses that were adequate for depletion of circulating cells. Clinical response appeared to correlate with dose of MoAb administered with progressive disease (52 mg), stable disease (104 mg), minor response (1,032 mg), and partial response (2,380 mg) observed in consecutive patients. The patient treated with the highest 1F5 dose achieved a 90% reduction in evaluable lymph node disease, but the duration of this remission was brief (six weeks). This study demonstrates that high doses of 1F5 can be administered to patients with negligible toxicity by continuous infusion and that clinical responses can be obtained in patients given greater than 1 g of unmodified antibody over a ten-day period.

Adult↗

Immunosuppression with monoclonal antibodies. A model to determine the rules for effective serotherapy.

Despite the range of available T cell specific monoclonal antibodies, there are no established rules to predict which might be immunosuppressive. We here describe a series of five rat monoclonal antibodies to a defined T cell antigen (mouse Thy-1) and evaluate their ability to immunosuppress mice. When compared with rabbit anti-lymphocyte globulin, only one of these monoclonal antibodies was able to delay skin allograft rejection and eliminate antibody responses to sheep red blood cells. This antibody was immunosuppressive following intra-peritoneal administration, even though it did not eliminate all of the T cells in vivo. Two factors may be relevant in determining the immunosuppressive properties of this reagent. First, the monoclonal antibody is of the rat IgG2b sub-class, and second, the specificity of the antibody is different to the other monoclonal antibodies in that it reacts with sub-populations of peripheral T cells, thymocytes and non-T cells. In practice, this suggests that to derive suitable monoclonal antibodies for human serotherapy, one should give attention to both the subclass and the fine specificity of the antibody for the target molecule.

Animals↗

Generation of human C3a, C4a, and C5a anaphylatoxins by protein A of Staphylococcus aureus and immobilized protein A reagents used in serotherapy of cancer.

Protein A (SpA) alone or immobilized on bacteria (e.g., Cowan strain I), collodion charcoal, or on Sepharose have been used in serotherapy of cancer in humans and experimental animals. Because SpA forms complexes with IgG that can activate complement, and the physiologic response during treatment often involves hypocomplementemia and reactions that are similar to those induced by anaphylatoxins, we used sensitive and specific radioimmunoassays to test the ability of SpA reagents to generate C3a, C4a, and C5a from human serum. The yield of anaphylatoxins depended on the dose of SpA, with the maximum generation of C3a (47 to 55 micrograms/ml) and C5a (1.4 to 1.9 micrograms/ml) being produced with levels of SpA that were maximally precipitated from serum. Maximum C4a levels (up to 15 micrograms/ml) were obtained at concentrations of SpA equal to or greater than the dose required to give optimal precipitation. The maximum concentrations of anaphylatoxins correspond to essentially quantitative conversions of C3 to C3a, C4 to C4a, and 40% of C5 to C5a after correction for levels found in serum incubated in pyrogen-free saline. Preformed insoluble complexes prepared from either serum or monomeric IgG also were capable of generating anaphylatoxins in fresh whole serum up to levels approximately equal to those observed in serum treated directly with an optimal amount of SpA. The preformed complexes from serum or IgG generated similar high concentrations of anaphylatoxins when carried through four sequential incubations with fresh serum, and complexes that contained approximately 1 microgram SpA were still active. Preincubating the insoluble complexes with chicken anti-SpA serum did not alter their activity. Incubation of serum with collodion charcoal coated with SpA, in a system that models the perfusion technique used to treat cancer, produced complexes that generated significant levels of C3a compared with levels found in serum passaged over albumin charcoal or in untreated serum. The C3a levels in serum from the albumin collodion charcoal were not significantly different from those found in untreated serum. Similar amounts of C3a, C4a, or C5a were observed in serum incubated with differing numbers of bacteria representing a strain of S. aureus rich in cell bound SpA (Cowan strain I) or a strain (Wood 46) deficient in SpA. This suggests that in intact bacteria, cell wall factors other than SpA (e.g., peptidoglycan) are predominantly responsible for generating anaphylatoxins.(ABSTRACT TRUNCATED AT 400 WORDS)

Anaphylatoxins↗

[Fall in the levels of circulating lymphoblasts caused by intravenous administration of the A50 monoclonal antibody in a patient with acute T-cell lymphoblastic leukemia. A step in the demonstration of serotherapy with monoclonal antibodies].

In an 8-year-old boy with acute lymphoblastic leukaemia not previously treated intravenous administration of a single 8 mg dose of a monoclonal antibody that recognizes an epitope restricted to the surface of mature T-cells resulted, within 20 hours, in a fall in circulating lymphoblasts from 200 000 to 70 000. No adverse clinical or biological reaction was detected and no antigenic modulation occurred at lymphoblast surface. This observation constitutes a first step in the complex development of effective serotherapy for malignant diseases, using monoclonal antibodies.

Animals↗

Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen.

A preliminary serotherapeutic trial was undertaken with a monoclonal antibody designated antibody 89 (Ab 89) directed against a lymphoma-associated antigen. In vitro studies demonstrated that Ab 89 could mediate complement-dependent lysis and macrophage adherence but not antibody-dependent cell-mediated cytotoxicity. To evaluate toxicity and therapeutic efficacy, two courses of Ab 89 were administered to a patient with an Ab 89-reactive tumor. Transient decreases in the number of circulating tumor cells and the appearance of circulating dead cells were noted with the infusion of Ab 89. Following administration of 150 mg or more of Ab 89, small amounts of antibody could be demonstrated on circulating tumor cells at a time when no free antibody was found in the serum. The inability to deliver a significant amount of Ab 89 to tumor cells in vivo is thought to be secondary to a circulating tumor antigen. Following each infusion, the amount of this blocking antigen decreased but could not be entirely cleared from the serum. This study provides preliminary evidence for the lack of clinical toxicity of a monoclonal antibody and identifies circulating blocking antigens as a significant obstacle to serotherapy.

Antibodies, Neoplasm↗