VARIABLE NEW ANTIGEN RECEPTOR (VNAR) ANTIBODIES AND ANTIBODY CONJUGATES TARGETING TUMOR AND VIRAL ANTIGENS

摘要

The antigen binding region of immunoglobulin new antigen receptor (IgNAR) antibodies found in cartilaginous fish is composed solely of a heavy chain, which makes it one of the smallest immunoglobulins in the animal kingdom. The reduced size allows the variable region (V_NAR domain) of this immunoglobulin to bind poorly exposed epitopes in target proteins. Construction of a naive phage-displayed V_NAR antibody library from six adult nurse sharks is described. Isolation and characterization of a panel of binders from the V_NAR library is also described. The V_NAR antibodies bind a variety of tumor antigens, including glypican-3 (GPC3), HER2 and PDl, and viral antigens, including the spike protein of Middle East respiratory syndrome (MERS) virus and severe acute respiratory syndrome (SARS) virus.