Protein engineering for targeted delivery of radionuclides to tumors

[摘要] (cont.) We engineered a high-affinity antibody fragment specific to DOTA and subsequently engineered a novel bispecific antibody (bsAb) construct with specificity for both DOTA and carcinoembryonic antigen (CEA). The bsAb exhibits retention of parental affinities, in vivo stability, and tumor targeting. The engineered PRIT approach was tested in a mouse tumor model and demonstrates excellent DOTA capture at the site of the tumor with the best 48 hour tumor to blood and tumor to kidney ratios reported to date for CEA targeting. The PRIT approach developed here can be easily applied to other disease targets and has the potential to impact clinical cancer radioimmunotherapy.

[发布机构] Massachusetts Institute of Technology