31-12-2020 дата публикации
Номер: US20200407457A1
Автор:
Dexian ZHENG,
Shuyong ZHANG,
Oudong PAN,
Chao ZHENG,
Wan ZHU,
Qingmei XIA,
ZHENG DEXIAN,
ZHANG SHUYONG,
PAN OUDONG,
ZHENG CHAO,
ZHU WAN,
XIA QINGMEI,
ZHENG, Dexian,
ZHANG, Shuyong,
PAN, Oudong,
ZHENG, Chao,
ZHU, Wan,
XIA, Qingmei
Принадлежит:
Provided is a broad-spectrum, efficient and anti-tumor anti-TRAILR2 antibody-toxin-conjugate (ADC, named Zapadcine-1(a, b, c, d) and Zapadcine-3(a, b, c, d, e)). Toxin with cytotoxic effect is linked to an anti-TRAILR2 humanized monoclonal antibody by means of a covalent bond by using disulfide bond bridging or conventional coupling technology and chemical linkers, so as to form an anti-TRAILR2 humanized antibody-toxin-conjugate. The ADC has the specificity of TRAILR2 positive tumors, and after conjugated to TRAILR2, the positive tumors can be endocytosed into lysosomes of tumor cells, and is degraded by means of proteases inside the lysosomes to release free micromolecule urotoxins, so that different TRAILR2 positive tumor cells are killed specifically, the tumor growth is suppressed, the tumor cells are even completely eliminated, and the tumor is cured. 1. An antibody-drug conjugate or the pharmaceutically acceptable salt or solvent compound thereof , wherein the antibody-drug conjugate comprises:(a) an antibody moiety; and(b) a coupling moiety coupled to the antibody moiety, which is selected from the group consisting of a detectable label, a drug, a toxin, a cytokine, a radionuclide, an enzyme, and a combination thereof;wherein, the heavy chain variable region of the antibody comprises the following three complementary determining regions CDRs:(H1) CDRH1, shown in SEQ ID NO: 1,(H2) CDRH2, shown in SEQ ID NO: 2, and(H3) CDRH3, shown in SEQ ID NO: 3;wherein, any one of the amino acid sequences in the above heavy chain variable region amino acid sequence also includes a derivative sequence optionally added, deleted, modified, and/or substituted with at least one amino acid, and capable of retaining the binding affinity of TRAILR2; and/orthe light chain variable region of the antibody comprises the following three complementary determining regions CDRs:(L1) CDRL1, shown in SEQ ID NO: 4,(L2) CDRL2, shown in SEQ ID NO: 5, and(L3) CDRL3, shown in SEQ ID NO: 6;wherein, ...
Подробнее