The ten commandments for immunotherapeutic drugs at the example of sulfur-containing agents.
Immunotherapeutic agents (IMT) are intended to restore or reequilibrate a faltering immune system. Levamisole was the first chemically defined IMT endowed with immunomodulatory effects. In order to clarify the mechanisms of its ambivalent activities, thiocompounds were tested for their ability to modify immune responses. All thiomidazoles are immunomodulatory drugs which dose-dependent effectiveness is related with the cholinergic-like influence of the imidazole moiety. The findings suggest also a relationship among thiodrugs between chemical structure and influence on the immune system. These studies lead to the development of sodium diethyldithiocarbamate (Imuthiol), as a non-toxic immunostimulant agent, specifically active on the T-cell lineage. Our studies unequivocally put forth on the specific requirements that are essential to characterize a potential IMT prior to clinical release: in vivo activities no immunosuppression through prolonged administration no antigenicity or hapten-like activity no carcinogenicity or tumor-promoting influence experimental route of administration related to that in humans assays in various animal strains pharmacokinetics chemical characterization known toxicities, teratogenesis, and mutagenesis assays on models of cancer, autoimmune diseases, immunodeficiencies, and infections. The results will allow to determine a range of doses, and predict most direct and secondary effects. They will also specify whether the agent is an adjuvant, a reticulostimulant, an immunomodulatory, an immunostimulatory, an immunorestorative, or an immunoregulating drug. Clinicians will therefore be provided with the data which are essential to perform useful clinical testing.
D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy; D004050:Ditiocarb / Q000627:therapeutic use*; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use*; D007107:Immune System / Q000187:drug effects*; D007153:Immunologic Deficiency Syndromes / Q000628:therapy; D007239:Infections / Q000628:therapy; D007978:Levamisole / Q000627:therapeutic use; D051379:Mice; D009369:Neoplasms / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D007093:Imidazoles; D007978:Levamisole; D004050:Ditiocarb