Targeting of tumor vasculature using radiolabelled antibody L19 against fibronectin ED-B
申请人:Philogen S.p.A.
公开号:EP1514561A1
公开(公告)日:2005-03-16
A specific binding member that binds human ED-B, wherein the specific binding member is labelled with an isotope selected from the group consisting of 76Br, 77Br, 123I, 124I, 131I and 211At and comprises an antigen-binding site that comprises an antibody VH domain and an antibody VL domain, wherein the antibody VH domain is selected from the group consisting of the L19 VH domain, and a VH domain comprising a VH CDR1, a VH CDR2 and a VH CDR3, wherein the VH CDR3 is the L19 VH CDR3 of SEQ ID NO. 3, the VH CDR1 is optionally L19 VH CDR1 of SEQ ID NO. 1, and the VH CDR2 is optionally L19 VH CDR2 of SEQ ID NO. 2; and wherein the antibody VL domain is optionally selected from the group consisting of the L19 VL domain, and a VL domain comprising a VL CDR1, a VL CDR2 and a VL CDR3, wherein the VL CDR3 is the L19 VL CDR3 of SEQ ID NO. 6, the VL CDR1 is optionally L19 VL CDR1 of SEQ ID NO. 4, and the VL CDR2 is optionally L19 VL CDR2 of SEQ ID NO. 5; the L19 VH domain and L19 VL domain sequences being disclosed in Pini et al. (1998) J. Biol. Chem. 273: 21769-21776; wherein the specific binding member comprises a mini-immunoglobulin comprising said antibody VH domain and antibody VL domain fused to εS2-CH4 and dimerized or comprises a whole IgG1 antibody molecule; also methods and uses employing such a specific binding member.
一种结合人类ED-B的特异结合成员,其中该特异结合成员标记有从76Br、77Br、123I、124I、131I和211At组成的同位素中选择的一种,并包括一个包含抗原结合位点的抗体VH结构域和抗体VL结构域,其中抗体VH结构域选自L19 VH结构域组,以及包括VH CDR1、VH CDR2和VH CDR3的VH结构域,其中VH CDR3是序列ID号为3的L19 VH CDR3,VH CDR1可以选择序列ID号为1的L19 VH CDR1,VH CDR2可以选择序列ID号为2的L19 VH CDR2;抗体VL结构域可以选择自L19 VL结构域组,以及包括VL CDR1、VL CDR2和VL CDR3的VL结构域,其中VL CDR3是序列ID号为6的L19 VL CDR3,VL CDR1可以选择序列ID号为4的L19 VL CDR1,VL CDR2可以选择序列ID号为5的L19 VL CDR2;L19 VH结构域和L19 VL结构域序列在Pini等人(1998)J. Biol. Chem. 273: 21769-21776中披露;其中该特异结合成员包括一个包含所述抗体VH结构域和抗体VL结构域的迷你免疫球蛋白融合到εS2-CH4并二聚化,或包括一个完整的IgG1抗体分子;还包括采用此类特异结合成员的方法和用途。