Targeted alpha therapy (TAT) using astatine-211 (²¹¹At), an alpha-emitting radionuclide, has gathered much attention as a next-generation cancer treatment that offers high selectivity and minimal side effects.In Japan, a domestic production system for ²¹¹At has been established, accelerating the development of ²¹¹At -labelled therapeutic agents for clinical application.

We have developed an ²¹¹At-labelled RGD peptide that has high affinity for α_vβ₃ integrin expressed on the surface of cancer cells. In tumour-bearing model mice, we confirmed that ²¹¹At-labelled RGD peptide exhibits high tumour accumulation and significant tumour growth inhibition. In this study, we focused on the potential of combining ²¹¹At-labelled RGD peptide therapy with immunotherapy to enhance its therapeutic efficacy.

We evaluated the therapeutic efficacy of combination therapeutic efficacy with ²¹¹At-labelled RGD peptide and an immune checkpoint inhibitor (anti-CTLA-4 antibody, αCTLA-4) using tumour-bearing mice. The results showed that the combination therapy significantly enhanced tumour growth inhibition and prolonged survival compared to each monotherapy. Furthermore, even with an ²¹¹At-labelled RGD peptide monotherapy, increased infiltration of immune cells, such as T cells, into the tumour tissue was observed, indicating that an anti-tumour immune response was induced. These findings suggest the potential of a synergistic treatment strategy that enhances therapeutic efficacy through anticancer immunity by combining ²¹¹At-labelled RGD peptide with immune checkpoint blockade.

These findings demonstrate the potential of a novel cancer therapy that combines TAT by ²¹¹At with immunotherapy. Further research is expected to focus on elucidating the detailed mechanisms of antitumor immune response and expanding preclinical studies.

Source: Kanazawa University