Successful treatment of hereditary angioedema with bradykinin B2‐receptor antagonist icatibant

The bradykinin B2 receptor antagonist icatibant has recently become available for treating hereditary angioedema. Our observations demonstrate icatibant to be effective and safe for the treatment of both, abdominal and cutaneous attacks in a practice setting beyond clinical studies.     

Recombinant antibodies for delivery of antigen: a single loop between beta-strands in the constant region can accommodate long, complex and tandem T cell epitopes

Recombinant antibodies are increasingly used for efficient delivery of T cell epitopes to antigen-presenting cells (APCs), both for vaccination purposes and for immune modulation. We have previously shown that recombinant antibodies can accommodate single T cell epitopes inserted into loops between beta-strands in constant (C) domains. Such recombinant antibodies have in addition been equipped with variable regions that target APCs for increased delivery of C region T cell epitopes. We here show that loop 6 (loop FG) in C(H)1 of human gamma 3 can be exchanged with (i) long T cell epitopes up to 37 amino acids, (ii) epitopes with complex secondary structure such as gluten epitopes with a type II polyproline helical confirmation and (iii) two tandemly linked T cell epitopes. T cell responses increased with T cell epitope elongation, presumably due to a positive influence of flanking residues. Recombinant antibodies targeted to either CD14 on monocytes or HLA-DP on monocytes and dendritic cells gave similar results and were 2-4 logs more efficient at stimulating human T cells than were non-targeted controls. Thus, single loops in C regions of recombinant antibodies seem versatile and may be used for delivery of lengthy, complex and multiple T cell epitopes to human APCs.