SEZ6-Targeted PET Imaging and Alpha-Particle Radioimmunotherapy is Effective for Detection and Treatment of Small Cell Lung Cancer.

SEZ6-targeted α-particle radioimmunotherapy induces complete tumor regression in small cell lung cancer models.

• Why it matters: Small cell lung cancer has a five-year survival rate of less than 10%, highlighting the urgent need for more effective targeted therapies. Understanding barriers to targeting SEZ6 could improve treatment strategies for neuroendocrine tumors like SCLC.
• What they did: Researchers developed a humanized anti-SEZ6 monoclonal antibody for PET imaging and radioimmunotherapy, evaluating its tumor uptake, receptor dynamics, and therapeutic efficacy in xenograft models, including dose optimization and combination with ATR inhibition.
• The result: Treatment with [225Ac]Ac-Macropa-SEZ6-Ab caused complete tumor regression, and co-administration with berzosertib enhanced efficacy at lower doses, demonstrating potent antitumor activity and identifying tumor SEZ6 shedding as a biological barrier to therapy.