Comment on “Production of multivalent protein binders using a self‐trimerization collagen‐like peptide scaffold”

Abstract

The recently published manuscript by Fan et al. (1) describes the generation of multivalent antibody fragments using collagen sequence-based peptides to drive multimerization. In 2006, our group reported in The International Journal of Cancer that fusion of the Nterminal association subdomain (50 residues) of murine collagen XVIII NC1, responsible for noncovalent trimerization of collagen XVIII alpha chains, to the C-terminus of a single-chain variable fragment (scFv) confers their natural trimeric state to the fused antibody (2). The homo-trimeric molecules were isolated in functional active form from the cell culture supernatant of gene-modified human cells and showed high stability in the presence of relevant proteinases (2). The scFv used recognizes an angiogenesis-associated laminin epitope (3) and inhibits tumor angiogenesis and growth in vivo (4). We demonstrated that trimeric scFv-NC1 bound to laminin, and was more effective in blocking capillary morphogenesis in vitro, and in preventing tumor growth in vivo than its monomeric version (2). Given the wide availability of Internet-based search engines, we regret the omission in the above mentioned paper of our original reference showing for the first time the ability of collagen-derived sequences to promote antibody trimerization.