MESOTHELIN DOMAIN-SPECIFIC MONOCLONAL ANTIBODIES AND USE THEREOF

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.

主权项

1. An isolated monoclonal antibody that binds mesothelin, wherein:
(i) the variable heavy (VH) domain of the antibody comprises a complementarity determining region (CDR) 1, a CDR2 and a CDR3 from SEQ ID NO: 13; and the variable light (VL) domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 15; (ii) the VH domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 9; and the VL domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 11; (iii) the VH domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 17; and the VL domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 19; (iv) the VH domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 21, or comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 29; and the VL domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 23; or (v) the VH domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 25; and the VL domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO: 27.