Single-Dose Cisplatin Pre-Treatment Enhances Efficacy of ROBO1-Targeted Radioimmunotherapy

• Published in: International journal of molecular sciences 2020-10, Vol.21 (20), p.7728
• Main Authors: Fujiwara, Kentaro, Koyama, Keitaro, Tsuji, Atsushi B, Iwanari, Hiroko, Kusano-Arai, Osamu, Higashi, Tatsuya, Momose, Toshimitsu, Hamakubo, Takao
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Blood; Blood cells; Body weight; Body weight loss; Cancer therapies; Cell cycle; Cell Line, Tumor; Chemotherapy; Cisplatin; Cisplatin - pharmacology; combination therapy; Dose-Response Relationship, Drug; Drug dosages; Histology; Histopathology; Humans; Immunoglobulin G; Injection; Lung cancer; Male; Medical prognosis; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms - pathology; Neoplasms - therapy; Pancytopenia; Pretreatment; Radiation therapy; Radioimmunotherapy; ROBO1; small-cell lung cancer; Survival; Treatment Outcome; Weight loss; Xenografts; Xenotransplantation; Yttrium isotopes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21207728

We previously reported that radioimmunotherapy (RIT) using Y-labeled anti-ROBO1 IgG ( Y-B5209B) achieved significant anti-tumor effects against small-cell lung cancer (SCLC) xenografts. However, subsequent tumor regrowth suggested the necessity for more effective therapy. Here, we evaluated the efficacy of combination Y-B5209B and cisplatin therapy in NCI-H69 SCLC xenograft mice. Mice were divided into four therapeutic groups: saline, cisplatin only, RIT only, or combination therapy. Either saline or cisplatin was administered by injection one day prior to the administration of either saline or Y-B5209B. Tumor volume, body weight, and blood cell counts were monitored. The pathological analysis was performed on day seven post injection of Y-B5209B. The survival duration of the combination therapy group was significantly longer than that of the group treated with RIT alone. No significant survival benefit was observed following the isolated administration of cisplatin (relative to saline). Pathological changes following combination therapy were more significant than those following the isolated administration of RIT. Although combination therapy was associated with an increase of several adverse effects such as weight loss and pancytopenia, these were transient. Thus, cisplatin pre-treatment can potentially enhance the efficacy of Y-B5209B, making it a promising therapeutic strategy for SCLC.