Rapid identity testing of antibody-based hot targeted radionuclide therapies by bio-layer interferometry.

Targeted Radionuclide Therapies (TRT) involve the tailored combination of a therapeutic radionuclide and a targeting molecule, as for instance antibodies or fragments thereof. Despite their short shelf-life, these drug products must meet stringent regulatory standards before use. We introduce a novel, efficient method utilizing Bio-Layer Interferometry (BLI) for rapid identity testing of TRT drug products in less than five minutes.

Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer.

Purpose: Prostate-specific membrane antigen (PSMA) is an attractive target for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC). PSMA-targeted alpha therapy (TAT) has shown early signs of activity in patients with prostate cancer refractory to beta radiation. We describe a novel, antibody-based TAT, the PSMA-targeted thorium-227 conjugate PSMA-TTC (BAY 2315497) consisting of the alpha-particle emitter thorium-227 complexed by a 3,2-HOPO chelator covalently linked to a fully human PSMA-targeting antibody.

Fully human antagonistic antibodies against CCR4 potently inhibit cell signaling and chemotaxis.

Background: CC chemokine receptor 4 (CCR4) represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs) and on tumor cells in several cancer types and its role in metastasis.

Methodology: Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis.