Application of Chemical Immunomodulators to the Treatment of Cancer and AIDS

Abstract

A number of potential advantages, development of promising new agents, and the discovery of synergy with cytokines or cell products continue to spur research into the application of chemical immunomodulators for the treatment of cancer and AIDS. In preclinical in vitro and in vivo systems, chemical immunomodulators definitely modulate the immune system and have therapeutic efficacy. Although clinical trials have shown the ability of these agents to modulate the human immune system, thus far chemical immunomodulators have generally not fulfilled the therapeutic promise generated in animal models for the treatment of human diseases. While the discrepancy in results between animal models and human trials is obvious, the basis is not apparent. Species differences in elimination kinetics, presentation of active drug at the site of action, and the development of tachyphylaxis have been postulated as reasons for the minimal activity of these agents in humans. In addition, the use of investigational techniques established for cytotoxic agents may not be appropriate for immunomodulators. As with any immunomodulator, determining an optimal immunostimulatory dose and schedule and applying the therapy to patients with minimal tumor burden would perhaps be more appropriate than use of a maximally tolerated dose in patients with advanced disease. A dose-immunological effect relationship has recently been demonstrated for levamisole at doses higher than those used for many years in levamisole trials (99). While research and clinical investigation have identified several potentially useful chemical immunomodulators, the elementary understanding of the biochemical mechanisms involved in immunoregulation remains basic. Future research must elucidate these mechanisms, particularly in humans, to maximize the benefits of chemical immunomodulators as single agents or combined with cytotoxic chemotherapeutic agents, surgery, radiation therapy, other immunomodulators, and antiviral agents.

Selenium nanoparticle-enriched Lactobacillus brevis causes more efficient immune responses in vivo and reduces the liver metastasis in metastatic form of mouse breast cancer

“…The spleen cell counts were adjusted to 2.5 × 10 6 cell/ml in RPMI1640 (Gibco Life Technologies, Germany) supplemented with 10% fetal bovine serum (Invitrogen, Paisley Germany), 100 μg/ml streptomycin, and 100 IU/ml penicillin (Sigma, Germany). These cells were then stimulated with 20 μg/ml of the tumor antigen (the amount was determined in a previous study) for 72 h [4] at 37°C in a humidified atmosphere of 5% CO 2 . The levels of IL-17 and IFN-γ in the spleen cell culture supernatants were determined using ELISA kits (R&D Systems, Minneapolis, MN), according to the manufacturer’s instructions.…”

“…Immunomodulatory agents are divided in two groups of immunosupressors and immunostimulators. Chemical immunomodulators like levamizole have been used in order to stimulate immune response against cancer and AIDS [4]. Natural immunomodulators like glucan or other oligosaccharide components which are mostly derived from microbial source are being applied to stimulate the immune response against cancers [5].…”

Immunomodulators as therapeutic agent

“…However, such tumor-specific antigens have been hard to find, and so many of the immune agents now in use do target healthy cells as well, but the hope is that these can later be rep laced. 7…”

Immunomodulatory Effects of the Meretrix Meretrix Oligopeptide (QLNWD) on Immune-Deficient Mice

“…There are many types of immunomodulators, such as bacterial preparations (e.g., lipopolysaccharide (LPS)), chemical preparations (e.g., cyclophosphamide (CTX)), and biochemical preparations (e.g., thymosin) [4]. However, some chemical immunomodulators have serious side effects, which not only have a specific inhibitory effect on the cause of immune diseases, but also have general inhibitory effects on normal tissue cells [5]. Inflammation, infection, tumors, organ bleeding, and loss of pregnancy have all been reported as being induced after the administration of chemical immunomodulators [6].…”