Year: 2005
Type: dissertation
Abstract: Recombinant proteins have made a surge in therapeutics for a variety of applications. Recently, monoclonal antibodies (mAbs) have received FDA approval for treatments including cancer, autoimmune diseases, asthma, and other conditions. Therapeutic mAbs require high affinity and specificity to antigen as well as pharmacokinetic properties that provide optimal interaction with target. The engineering of recombinant antibodies tailors these parameters to specific applications for therapy. This dissertation describes the development of therapeutic antibody fragments targeting the protective antigen (PA) component of the secreted anthrax exotoxin. High-affinity, single-chain antibody fragments (scAbs) expressed in E. coli were modified to enhance serum half-lives for therapeutic application as anti-toxins. By targeting PA, these constructs were able to provide passive immunity against anthrax lethal toxin and spore inhalation challenges in animal models. The success of these fragments provides evidence that anti-toxin therapies do not require high cost, mammalian-expressed mAbs. In addition, immunity was shown in the absence of a glycosylated Fc region of mammalian-expressed immunoglobulins which is known to activate immune-mediated functions responsible for clearance of pathogens. These results indicate that microbial production of antibody fragments could provide a low cost alternative to mammalian culture for potential antibody reagents and therapeutics.
Author: George Robert Mabry
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1857771280