Harnessing Targeted Alpha Therapy: A Promising Approach for CD37 Positive CLL and NHL Treatment

Chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) are prevalent in the United States, with over 90,000 new cases annually. The conventional treatment involves immuno-chemotherapy, which, despite initial success, often leads to patient relapse and reduced treatment efficacy over time. As a result, there is a growing interest in alternative therapies, particularly targeting CD37, a protein found on mature B lymphocytes and B-cell malignancies.

A novel approach involves targeted alpha therapy (TAT), which utilizes the CD37-specific antibody NNV003 linked to the alpha-particle-emitting isotope ^212Pb. This therapy leverages the high energy deposition of alpha particles, which can cause DNA damage and cell death, while minimizing harm to surrounding tissues.

In a study, the efficacy and safety of a single ^212Pb-NNV003 dose were examined in human models of Burkitt's lymphoma and CLL. The treatment was administered to mice with disseminated tumors, and a control group received an unspecific, ^212Pb-labeled antibody. The results showed that ^212Pb-NNV003 had a favorable toxicity profile, with no acute hematological toxicity observed. Mice treated with doses of 5, 10, or 15 μCi of ^212Pb-NNV003 experienced only a temporary decrease in platelet counts, which recovered fully within 20 days.

Furthermore, a single intravenous injection of 10, 15, or 20 μCi of ^212Pb-NNV003 resulted in 70%, 90%, and 100% of mice with CLL being tumor-free 20 weeks after cell injection. Similarly, doses of 2.5, 5, and 7.5 μCi led to over 80% of mice with Burkitt's lymphoma being tumor-free 15 weeks post-injection.

The preclinical findings indicate that TAT with ^212Pb-NNV003 is both safe and effective, offering a promising new treatment for CD37-positive CLL and NHL.