Considerations for the development of therapeutic monoclonal antibodies.

An increasing number of Investigational New Drug (IND) applications for therapeutic monoclonal antibodies (mAbs) have been submitted to US FDA over the past several years. Monoclonal antibodies and related products are under development for a wide range of indications. In addition, the diversity of antibody-related products is increasing including IgG2/IgG4 subclasses and engineered Fc regions to enhance or reduce antibody effector functionality. Recent findings highlight the need to more fully characterize these products and their activity. Advances in product characterization tools, immunogenicity assessments, and other bioanalytical assays can be used to better understand product performance and facilitate development.

Immunization with meningococcal polysaccharide-tetanus toxoid conjugate induces polysaccharide-reactive T cells in mice.

T cell clones were generated from mice immunized with a meningococcal group C (alpha2 --> 9-sialic acid) polysaccharide-tetanus toxoid (MCPS-TT) conjugate. Many clones were found to be specific for tetanus toxoid (TT), however, clones reactive with MCPS-TT and polysaccharide (PS) were isolated. Two clones were specific for MCPS and two cross-reacted with Escherichia coli K1-PS (alpha2 --> 8-sialic acid). Both TT and PS reactive clones were CD4+ and CD8-. TT and MCPS-TT-specific T cell clones were major histocompatibility complex (MHC) restricted, however, the PS-reactive clones were not. Both MHC-restricted TT clones and non-restricted PS clones, however, were dependent on contact with antigen presenting cells (APC) for maximal stimulation. The data suggest that multivalent repeating epitopes on PS antigen (Ag) can overcome the need for MHC restricted interactions, but not the requirement for cell-cell contact.