Abstract
Recently, more and more research of therapeutic drugs based on peptide development was respected by scientists. Pharmaceutical and biotechnological industries had also invested a lot of funds in discovering this kind of drug. However, only a few therapeutic peptides have been approved for clinical application. These disappointing results were not due to the lack of inherent biological potency of the peptide drugs but to the insufficient bioavailability in patients. Some studies promoted the efficacy of peptide drugs by means of increased their half-life in blood. In this research, we evaluated the modulation of immunological function by three therapeutic peptides, Alloferon, Thymosin-□1 and Allofron-6C. Alloferon and Thymosin-□1 were isolated from insects and bovine thymic hormone. Previous studies indicated that they increased the the cytotoxicity of natural killer (NK) cell, induced the production of interferon, improved the survival rate on mice infected with influenza virus and inhibited the growth of tumors. We designed another therapeutic peptide, Allofron-6C, by adding an acyl chain consist of six carbon units to the carboxyl end of Alloferon. NK cytotoxicity assay, phytohemagglutinin (PHA) induced T cell proliferation assay, PHA induced interferon (IFN) production assay and adjuvanticity assay were used to examine the immunological function modulated by these therapeutic peptides. The result showed that the cytotoxicity of NK cell was significantly increased after NK cell pre-treated with Alloferon-6C for 4 hours, suggesting that the ex vivo half-life of Alloferon-6C was longer than Alloferon and Thymosin-α1. PHA induced T cell proliferation assay and PHA induced IFN production assay revealed that Thymosin-α1 was the potent one to stimulate T cell proliferation and IFN production. The adjuvanticity assay of therapeutic peptides manifested that high dose of Alloferon could elevate the level of antibody and T cell against BSA in vivo as well as Incomplete Freund’s adjuvant, a commercial adjuvant. Thus, we considered that Alloferon can be used as a new adjuvant.