New radioimmunotherapy approach eliminates cancer stem cells in preclinical models of ovarian cancer

A new radioimmunotherapy approach has been shown to successfully eliminate cancer stem cells (CSCs) in preclinical models of ovarian cancer, outperforming the current gold standard. This research, published in the July issue of The Journal of Nuclear Medicine, lays the foundation for further development of radionuclide therapies targeting CSCs, offering renewed hope for more effective treatment options and improved outcomes for patients.

CSCs are highly tumorigenic, self-renewable cells that play a key role in tumor relapse, metastasis, and therapy resistance. Although the clinical significance of eliminating CSCs is clearly recognized and CSC immunotherapies have been examined in preclinical and clinical evaluations, the development of such therapies remains a challenge. 

Radioimmunotherapy enables precise, target-specific delivery of particulate radiation to cancer-associated antigens, while minimizing off-target accumulation and increasing tumor retention and irradiation, which makes it a promising choice for targeting CSCs. Our study sought to investigate the effectiveness of a new radionuclide Terbium-161 (¹⁶¹Tb) for eradicating CSCs due to emission of short-ranged conversion and Auger electrons-besides beta-minus particle-successfully eliminated ovarian CSCs in contrast to Lutetium-177 (¹⁷⁷Lu).”

Jürgen Grünberg, PhD, senior scientist at the Center for Radiopharmaceutical Sciences, Center for Life Sciences at the Paul Scherrer Institute in Villigen, Switzerland

Researchers identified CSC-associated biomarkers (L1CAM⁺/CD133⁺) in an ovarian cancer sample and then created radiolabeled immunoconjugates with ¹⁷⁷Lu or ¹⁶¹Tb to target these CSCs. The cytotoxicity of the radioimmunoconjugates (¹⁷⁷Lu-DOTA-chCE7 and ¹⁶¹Tb-DOTA-chCE7) was measured by cell proliferation assays in vitro and in xenografted mouse models in vivo.

¹⁶¹Tb-DOTA-chCE7 showed significantly increased cytotoxicity, compared with ¹⁷⁷Lu-DOTA-chCE7, eliminating all ovarian CSCs and tumor cells differentiated from the CSCs in vivo.

“This signifies a pivotal step toward the translation of ¹⁶¹Tb-based therapies into clinical application,” noted Tihomir Todorov, PhD, junior scientist at the Center for Radiopharmaceutical Sciences, Center for Life Sciences at the Paul Scherrer Institute. “Targeted radionuclide therapies with ¹⁶¹Tb could support personalized medicine leading to advancements in cancer care including eradication of resistant CSCs and increased therapeutic efficacy alongside improved diagnosis, detection, and treatment monitoring.”