Novel Diagnostic and Therapeutic Immunologic Strategies to Overcome Infectious, Oncologic and Neurodegenerative Disorders

In the scope of viral, oncologic, inflammatory and neurodegenerative diseases, animal models have been used to assess novel immunology based therapeutic strategies, such as the use of new generation monoclonal antibodies to treat immunodeficiency, lymphoma and neurodegenerative disorders. Here we describe the methods used in the development of engineered single domain antibodies (sdAbs) of rabbit origin against different antigenic targets using techniques that include rabbit immunization, construction of antibody libraries and selection by phage display. The potential of these antibodies as therapeutic tools is vast, varying with the antigen they target. They can be potent anti-viral products, if they are directed against viral spike glycoproteins, or anti-tumor cytotoxic reagents, if they target a tumor specific antigen, or precise therapeutic carriers, able to deliver pharmaceutical agents to locations where their antigen can be found. Applications of these methods are addressed in this review, exemplified with current work pursued in our lab. Namely development of: 1) specific recombinant sdAbs against the gp120 HIV-1 glycoprotein; 2) recombinant sdAbs and small molecules for diagnosis and treatment of naturally occurring canine lymphoma; and 3) recombinant sdAbs for brain targeting and drug delivery across the Blood-Brain Barrier.