Deimmunization of monoclonal antibodies.

Immunogenicity is a major limitation to therapy with certain monoclonal antibodies and proteins. A major driver for immunogenicity is the presence of human T-cell epitopes within the protein sequence which can activate helper T-cells resulting in the sustained production of antibodies and neutralization of the therapeutic effect. Deimmunization is a new technology for location and removal of T-cell epitopes through the combined use of immunological and molecular biology techniques. In the case of deimmunization of antibodies, mutations to remove T-cell epitopes can generally be introduced without significantly reducing the binding affinity of the antibody. Typically, "deimmunized" antibodies are created with human constant regions and by expression of genes encoding these antibodies in mammalian cells. This chapter details a method for creation of a deimmunized antibody for production in mammalian cells.

The development of a modified human IFN-alpha2b linked to the Fc portion of human IgG1 as a novel potential therapeutic for the treatment of hepatitis C virus infection.

Interferon-alpha (IFN-alpha), in conjunction with ribavirin, is the current standard for the treatment of chronic hepatitis C virus (HCV) infection. This treatment requires frequent dosing, with a significant risk of the development of anti-IFN-alpha neutralizing antibodies that correlates with lack of efficacy or relapse. We have developed an IFN-alpha linked to the Fc region of human IgG1 for improved half-life and less frequent dosing. We have also identified, using a human T cell proliferation assay, three regions of IFN-alpha2b that are potentially immunogenic, and a variant containing a total of six mutations within these regions was made. This variant was made as a fusion to Fc either with or without a flexible linker between the fusion partners. Both configurations of the variant were less active than native IFN-alpha alone, although the variant containing the flexible linker had in vitro antiviral activity within the range of other modified IFN-alphas currently in clinical use. Peptides spanning the modified regions were tested in T cell proliferation assays and found to be less immunogenic than native controls when using peripheral blood mononuclear cells (PBMCs) from both healthy individuals and HCV-infected patients who had been treated previously with IFN-alpha2b.

The lactic acid bacteria: a literature survey.

The purpose of this review article on the lactic acid bacteria grew from an early curiosity and a desire to convey and impart the broad scope of literary information on their functions as starter cultures, in the manufacture of fermentation products such as dairy products and alcoholic beverages, as well as their contribution to better health. This review article is an attempt to empower the reader and to circumvent the difficult task in acquiring and elucidating a large body of information. The intent is to familiarize the reader with the various lactic species, their habitat or source, associated food, physiological characteristics, colonial morphology, biochemical characteristics, culture media (enrichment, nonselective, and selective), classic description, and taxonomy. This review provides information on Lactobacillus, Lactococcus, Leuconostoc, Pediococcus, Carnobacterium, and Enterococcus. Trends are presented, such as the use of nisin to extend food shelf-life and the current research premise that Probiotic strains may alter the intestinal flora and thus prevent intestinal wall penetration by pathogens.