RECOMBINANT, SINGLE-CHAIN, TRIVALENT TRI-SPECIFIC OR BI-SPECIFIC ANTIBODY DERIVATIVES

摘要

The present invention relates to a nucleic acid molecule encoding a polypeptide, wherein the polypeptide comprises (a) a first immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to an antigen expressed on tumour cells; (b) a second immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to an antigen expressed on tumour cells; and (c) a third immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to an effector cell antigen, wherein the effector cell is selected from the group consisting of NK cells, neutrophilic granulocytes, monocytes and macrophages; wherein at least one of the antigens expressed on tumour cells and bound by the immunoglobulin domain of (a) or (b) is an antigen expressed on tumour stem cells and/or on tumour precursor or progenitor cells; and wherein the ratio of immunoglobulin domains binding to antigens expressed on tumour cells and those binding to effector cell antigens is at least 2:1. The present invention furthermore relates to a vector comprising the nucleic acid molecule of the invention, a non-human host transformed with the vector of the invention, a method of producing a polypeptide comprising culturing the host of the invention under suitable conditions and isolating the polypeptide produced and a polypeptide encoded by the nucleic acid molecule of the invention or produced by the method of the invention. In addition, the present invention relates to diagnostic and pharmaceutical compositions and methods for treating tumours.