Radioimmunotherapy for CD133 positive cancer stem cells inhibits tumor development in nude mice

Objectives: Accumulating evidences indicate that cancer stem cells (CSCs) are the route of tumor drug resistance, radio-resistance or distant metastasis, hence, it's essential to eliminate CSCs in order to cure cancer completely. The purpose of this study was attempted to utilize radioimmunotherapy (RIT) to target CD133 positive colonic CSCs and observe whether it has some effect for tumor developing. Methods: Two related studies were implemented. One was designed to assess the maximum tolerated dose (MTD) of HCT116 tumor bearing nude mice with escalating doses of 131I-AC133.1 mAb, and the other was for studying the therapeutic efficacy of RIT with 131I-AC133.1 mAb. 131I was radiolabeled to AC133.1 mAb by conjunction to N-succinimidyl-3-tri-n-butylstannyl, and the product was named as 131I-AC133.1 mAb. For RIT trials, animals were randomly divided into 4 groups with 6 each group, and they were respectively injected with 131I-AC133.1 mAb (16.65 MBq/100μl), AC133.1 mAb (173.1 μg/100μl), saline (100 μl), and uncorrelated IgG1 was as isotype controls. Biodistribution studies were performed at 1, 3, 5, 7 and 9 days after injection of 131I-AC133.1 mAb. Flow cytometry and HE staining were also conducted to verify the expression of CD133 and tumor tissue. Results: The radiospecific activity of 131I-AC133.1 mAb was 77.7 KBq/μg to 96.2 KBq/μg. Scatchard analyses of the binding data revealed that the affinity constant for AC133.1 mAb was (4.76 ± 0.30) x10-8 M (n=3), and the nonspecific binding was less than 2%. The radiochemical purity of the labeled antibody is 94.05% ± 1.53% (n=3). The MTD of HCT116 tumor bearing nude mice was 16.65 MBq. The tumor volume doubling time of 131I-AC133.1 mAb group (9.91 ± 0.41) d was longer than other groups (6.29 ± 0.78 d, 7.31 ± 0.68 d, and 7.89 ± 0.30 d for saline group, 131I-IgG1 group, and AC133.1 mAb group, respectively). The difference had much significance (P