Fibroblast activation protein targeted radiotherapy induces an immunogenic tumor microenvironment and enhances the efficacy of PD-1 immune checkpoint inhibition.

ABSTRACT:

Purpose

FAP is a membrane-bound protease under investigation as a pan-cancer target, given its high levels in tumors but limited expression in normal tissues. FAP-2286 is a radiopharmaceutical in clinical development for solid tumors that consists of two functional elements: a FAP-targeting peptide and a chelator used to attach radioisotopes. Preclinically, we evaluated the immune modulation and anti-tumor efficacy of FAP-2287, a murine surrogate for FAP-2286, conjugated to the radionuclide lutetium-177 (¹⁷⁷Lu) as a monotherapy and in combination with a PD-1 targeting antibody.

Methods

C57BL/6 mice bearing MCA205 mouse FAP-expressing tumors (MCA205-mFAP) were treated with ¹⁷⁷Lu-FAP-2287, anti-PD-1, or both. Tumor uptake of ¹⁷⁷Lu- FAP-2287 was

SUBMITTER: Zboralski D 

PROVIDER: S-EPMC10317891 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature