DOTAM-binding site on the CEA-targeted bispecific antibody (CEA-PRIT 2.0)

The DOTAM-binding site on the CEA-targeted bispecific antibody is an engineered molecular docking site used in pre-targeted radioimmunotherapy (PRIT). This site is generated through the assembly of two complementary SPLIT antibodies (SeParated v-domains LInkage Technology) that each carry half of a high-affinity anti-DOTAM variable domain (VH or VL). These antibodies are designed to bind to Carcinoembryonic Antigen (CEA), a protein highly expressed in various solid tumors such as colorectal and pancreatic cancers. Upon binding to adjacent CEA molecules on the tumor cell surface, the VH and VL domains associate to form a functional receptor for the DOTAM (1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane) chelator. This artificial receptor then captures subsequently administered radiopharmaceuticals, such as 212Pb-DOTAM, allowing for the localized delivery of potent alpha-particle radiation. This strategy, often referred to as CEA-PRIT 2.0, is intended to improve the therapeutic index by decoupling the slow tumor-targeting phase of the antibody from the rapid delivery and clearance of the radioactive payload.

Other names

Pb-DOTAM binding siteanti-DOTAM VH/VL complexSPLIT antibody binding siteTA-split-DOTAM-VH/VLCEA-targeted SPLIT PRIT

Pre-targeted radioimmunotherapy (PRIT). The system utilizes two complementary SPLIT (SeParated v-domains LInkage Technology) antibodies that each carry half of a high-affinity anti-DOTAM variable domain. These antibodies bind to Carcinoembryonic Antigen (CEA) on the tumor cell surface, where they assemble to form a functional DOTAM-binding site. This site then captures subsequently administered radiopharmaceuticals, such as 212Pb-DOTAM, for localized alpha-particle therapy.