公开(公告)号：US20160229919A1

公开(公告)日：2016-08-11

申请号：US15141006

申请日：2016-04-28

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Ira H. Pastan ,  Yen T. Phung ,  Yifan Zhang ,  Wei Gao ,  Raffit Hassan

IPC分类号： C07K16/30 ,  A61K49/00 ,  G01N33/574 ,  A61K47/48 ,  C07K14/725 ,  C07K16/46 ,  C07K16/28 ,  A61K51/10

CPC分类号： C07K16/3023 ,  A61K39/395 ,  A61K47/6803 ,  A61K47/6829 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6857 ,  A61K47/6869 ,  A61K49/0058 ,  A61K51/1054 ,  A61K2039/505 ,  C07K14/7051 ,  C07K16/28 ,  C07K16/30 ,  C07K16/468 ,  C07K2317/24 ,  C07K2317/31 ,  C07K2317/34 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/624 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/30 ,  C07K2319/55 ,  G01N33/574 ,  G01N33/57492 ,  G01N2333/705

摘要： Described herein is the use of rabbit hybridoma technology, along with a panel of truncated mesothelin domain fragments, to identify anti-mesothelin mAbs that bind specific regions of mesothelin. In one aspect of the present disclosure, the rabbit mAbs bind an epitope that is not part of Region I. In particular, the identified mAbs (YP187, YP223, YP218 and YP3) bind either Region II (391-486), Region III (487-581) or a native conformation of mesothelin with subnanomolar affinity. These antibodies do not compete for binding with the mesothelin-specific immunotoxin SS1P or mesothelin-specific antibody MORAb-009. In another aspect, disclosed is a high-affinity rabbit mAb that binds Region I of mesothelin (YP158). YP158 binds native mesothelin protein in cancer cells and tissues with high affinity and specificity.

摘要翻译： 本文描述的是使用兔杂交瘤技术以及一组截短的间皮素结构域片段来鉴定结合间皮素特异性区域的抗间皮素mAb。 在本公开的一个方面，兔mAb结合不是区域I的表位。特别地，所鉴定的mAb（YP187，YP223，YP218和YP3）结合区域II（391-486），区域III（ 487-581）或具有亚纳摩尔亲和力的间皮素的天然构象。 这些抗体不竞争与间皮素特异性免疫毒素SS1P或间皮素特异性抗体MORAb-009的结合。 另一方面，公开了一种结合间皮素区域I（YP158）的高亲和力的兔单克隆抗体。 YP158以高亲和力和特异性结合癌细胞和组织中的天然间皮蛋白。

公开(公告)号：US20220064324A1

公开(公告)日：2022-03-03

申请号：US17421334

申请日：2020-01-02

申请人： The U.S.A., as represented by the Secretary, Department of Health and Human Services

发明人： Mitchell Ho ,  Ira H. Pastan ,  Jessica D. Hong ,  Nan Li

IPC分类号： C07K16/30 ,  C07K14/705 ,  C07K14/725 ,  A61K47/68 ,  C07K16/28 ,  A61K47/69 ,  C07K14/715 ,  C07K14/71 ,  A61P35/00

摘要： Camel single-domain monoclonal antibodies that specifically bind human and mouse mesothelin are described. Chimeric antigen receptor (CAR) T cells and antibody conjugates based on the mesothelin-specific antibodies are also described. The disclosed CAR T cells, mesothelin-specific antibodies and conjugates thereof can be used, for example, in the diagnosis or treatment of mesothelin-positive cancers.