TAT-10: Pharmacokinetic Profiling and Therapeutic Efficacy of Alpha-emitter Labeled Ant-PD1.1 Antibodies in an Immune Competent Transgenic Breast Cancer Model

Kanazawa, Japan (UroToday.com) Normally tumors are vulnerable from T cells in the body’s  immune system. Some tumors have the ability to express Programed cell Death Ligand 1 (PD-L1) which inactivates the T cells allowing the tumor to survive. Previous studies have shown that treatment with anti-PD-1 antibodies have been effective in reducing many cancers including breast cancer. The aim of this study is to investigate if the anti-PD-1 immunotherapy can be enhanced when combined Ac225 targeted alpha therapy.

To study the pharmacokinetics, 8-10 week old female mice with NT2.5 tumors were injected with the targeted imaging agent In111-DTPA-anti-PD-L1-BC (0.37 MBq) at antibody concentrations of 1-10 mg/kg. Ex-vivo biodistributions were determined at 1,6,24,72, and 144 hours post injection. Short term, the spleen showed higher uptake at lower doses, blood uptake was almost independent of dosage, and liver slightly higher uptake at low dose.

For therapeutic studies, mice were injected 3 days after anti-PD1 antibody injection with either Ac225-DOTA-anti-PD1-BC (15 kBq, 3 mg/kg), or unconjugated antibody at the same concentration, or saline.  The Ac225 group showed a significant increase in median survival (63 days, p > 0.05) compared to the saline group. Maximum tolerated dose studies show that doses up to 37 kBq are well tolerated so future studies could go to higher doses.

Presented By: Jessie Nedrow from Johns Hopkins University, Baltimore, MD

Written By: William Carithers, Lawrence Berkeley National Laboratory

at the 10th International Symposium on Targeted Alpha Therapy (TAT-10)  May 31 - June 1, 2017 - Kanazawa, Japan.
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