Prevention of oncogenic viral infections in mice with CGP 11637, a synthetic muramyl dipeptide analog

Abstract

The efficacy of N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (nor-MDP) in controlling viral oncogenesis in mice was investigated. The tumors studied were blood cell malignancies induced by Friend Muramyl dipeptide (MDP), N-acetyl-muramyl-L-alanyl-Disoglutamine, a dipeptide derivative of muramic acid (the 3-0-D-lactyl ether of D-glucosamine), is a typical bacterial cell wall constituent that represents the minimal sequence of peptidoglycans that still retains the full activity of Freund complete adjuvant in augmenting humoral immune responses (17,(20)(21)(22)31).A series of synthetic MDP analogs have been synthesized, and it has been found that by substitution of component carbohydrates and amino acids, pyrogenicity and other inflammatory and toxic side effects of MDP can be diminished or totally eliminated without loss of effectiveness (5,8,31). Synthetic MDP and its analogs have been shown to act as macrophage activators (4,9,10,13,26,28,29,32,33) and to effect some control of neoplastic spread in experimental systems as well as in various viral, bacterial, and fungal infections (2, 9, 10, 13-15, 18, 20-22, 24, 29).Since MDP and most of its analogs are highly soluble in water, intravenous administration in high doses, use of minipumps, and encapsulation in multilamellar vesicle liposomes have been utilized to increase the adjuvant activity of the compounds. Stevens and associates (30) utilized an emulsion injected subcutaneously (s.c.) for delivery of an immunogen containing nor-MDP (N-acetyl-nor-muramyl-Lalanyl-D-isoglutamine) as an adjuvant. This system apparently released the water-soluble components of the vaccine gradually. We used the same system of administration to study the effects of nor-MDP on viral oncogenesis in mice. MATERIALS AND METHODSReagents. Synthetic MDP analog CGP 11637 (nor-MDP) was a gift

Critical Review of Preclinical Approaches to Evaluate the Potential of Immunosuppressive Drugs to Influence Human Neoplasia

“…107 The assay is conducted over many months with 20 animals per group and the number and size of the resultant tumors measured. 108 Because many oncogenic viruses are immunosuppressive, 109 understanding the effects of an immunotoxicant could be problematic.…”

Human chorionic gonadotropin (hCG), the hormone of life and death: a review

“…hCG is soluble ad infinitum . Acevedo and his co‐workers have already used this slow release form of administration to eliminate virus induced leukemias and lymphomas (99), so the possibility exists for its use in the treatment of AIDS.…”