PubMed · 7348124
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N Mouillac-Gambarelli, P J Weiller. 1981. [Immunostimulants].. https://pubmed.ncbi.nlm.nih.gov/7348124/
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BACKGROUND: Currently, immunotherapy with Bacillus Calmette-Guerin (BCG) is the most effective treatment for superficial bladder carcinoma, but treatment-related toxicity may limit its use in some patients. Alternative treatments are needed for patients who fail to respond to BCG immunotherapy. Allium sativum (AS), or garlic, is known to have a broad range of biologic activities, including immune stimulation and reported antitumor activity. For these reasons, the authors conducted a series of experiments designed to explore the possible therapeutic effects of AS in the MBT2 murine bladder carcinoma model. METHODS: C3H/HeN mice were randomized prior to initiation of each experimental protocol. Mice received 1 x 10(3) MBT2 cells in 0.1 mL RPMI-1640, administered subcutaneously into the right thigh, on Day 0 of the experiment. AS was injected at the site of tumor transplantation on Day 1 and at 2- to 7-day intervals up to Day 28. To evaluate the effects of oral AS in this model, treatment was initiated 30 days prior to tumor inoculation and continued for 30 days after tumor inoculation. Animals in all experiments were followed for tumor incidence, tumor growth, and survival. RESULTS: In the initial experiments, subcutaneous AS significantly reduced tumor volume compared with the saline control (P < 0.05). Unfortunately, treatment-related death was also observed, requiring reduction in the total dose of AS. Animals that received 5 weekly immunizations of AS (5 mg, 5 mg, 1 mg, 1 mg, and 1 mg; cumulative dose = 13 mg) had significantly reduced tumor incidence, tumor growth, and increased survival when compared with animals that received the saline control. No treatment-related deaths were observed with this treatment schedule. To determine whether systemic AS administration might be effective, orally administered AS was tested at doses of 5 mg, 50 mg, and 500 mg per 100 mL of drinking water. Mice that received 50 mg oral AS had significant reductions in tumor volume (P < 0.05) when compared with animals that received the saline control, and mice that received 500 mg oral AS had significant reductions in both tumor volume and mortality (P < 0.05). CONCLUSIONS: The significant antitumor efficacy of subcutaneous and oral AS warrants further investigation and suggests that AS may provide a new and effective form of therapy for transitional cell carcinoma of the bladder.
In the course of examining epitope-specific CTL responses to intramuscular plasmid DNA immunization with influenza nucleoprotein (NP)-expressing vectors, a nonimmunogenic mutant NP (NP(o)) was identified. The coding region of NP(o) differed from the wild-type A/PR/8/34 NP sequence (designated NP(v)) by three amino acid alterations in the carboxyl-terminal portion of the molecule remote from the H-2K(d) epitope (147-155) being monitored. Correction of these mutations restored the immunogenicity of the native sequence, indicating that sequence alterations remote from the CTL epitope in question can profoundly influence its immunogenicity. In an effort to identify general, nonstructural means of enhancing the CTL response to weak plasmid DNA immunogens, vectors were constructed expressing NP(o) in tandem with the costimulatory molecules B7-1 or B7-2. Co-linear expression of NP(o) with B7-2, but not B7-1, significantly increased the NP epitope-specific CTL response. In addition, coinjection of these NP(o) plasmids with granulocyte-macrophage CSF- and/or IL-12-expressing vectors also restored near native NP-specific CTL responses. Thus, the coexpression of certain costimulatory molecules and/or cytokines, in concert with a non-self gene delivered as an intramuscular plasmid DNA immunogen, can significantly enhance Ag-specific CTL responses.
High-dose intravenous immune globulin (IVIg) has emerged as an important therapy for various neurologic diseases. Different interpretations of clinical trial results; the expected benefit of IVIg compared with that of alternate therapies; and issues about IVIg's safety, cost, and mechanisms of action have raised concern and uncertainty among practitioners. To clarify these areas, this paper examines the clinical, serologic, and immunologic data on more than 110 patients with various autoimmune neurologic diseases who received IVIg during the past 6 years at the National Institute of Neurological Disorders and Stroke. It also reviews work by other investigators on the efficacy, risks, benefits, and mechanisms of the action of IVIg in these diseases. In controlled clinical trials, IVIg has been effective in treating the Guillain-Barré syndrome, multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy, and dermatomyositis. In other controlled or open-label trials and case reports, IVIg produced improvement in several patients with the Lambert-Eaton myasthenic syndrome and myasthenia gravis but had a variable, mild, or unsubstantiated benefit in some patients with inclusion-body myositis, paraproteinemic IgM demyelinating polyneuropathy, certain intractable childhood epilepsies, polymyositis, multiple sclerosis, optic neuritis, and the stiff-man syndrome. The primary adverse reaction was headache; aseptic meningitis, skin reactions, thromboembolic events, and renal tubular necrosis occurred rarely. The most relevant immunomodulatory actions of IVIg, operating alone or in combination, are inhibition of complement deposition, neutralization of cytokines, modulation of Fc-receptor-mediated phagocytosis, and down-regulation of autoantibody production. Therapy with IVIg is effective for certain autoimmune neurologic diseases, but its spectrum of efficacy has not been fully established. Additional controlled clinical trials are needed.