Developments in CRM197 Glycoconjugates for Anticancer Vaccines

Abstract

The concept of using glycoconjugates to induce immunological responses to a carbohydrate hapten was reported in 1929 by Avery and Goebel [1]. However, glycoconjugate vaccines would not be revisited as therapeutic and prophylactic agents against bacterial infections until the 1970’s and early 1980’s [2-4]. Prior to these interests in glycoconjugates, licensed antibacterial vaccines consisted of isolated capsular polysaccharides which were efficacious in adults but failed to induce protection in high risk populations such as infants and children [5,6]. Glycoconjugate vaccines consist of a bacterial capsular polysaccharide conjugated to an immunogenic carrier molecule such as keyhole limpet hemocyanin (KLH), diptheria toxin (DT), tetanus toxoid (TT), cross-reactive material 197 (CRM197), as well as others [7-9]. This conjugate vaccine strategy is necessary due to the T cell independent nature of carbohydrates that have nominally elicited low affinity, short lived IgM antibodies with the exception of zwitterionic polysaccharides (ZPSs) [10-13]. Glycoconjugates are able to effectively bind to the MHCI and/or MHCII molecule on antigen presenting cells (APCs). This cellular interaction with the carbohydrate conjugate allows for the development of T cell mediated responses, and consequently leads to helper T cells (Th) which induce antibody isotype switching and immunological memory [14].