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. 2020 Oct 19;21(20):7728.
doi: 10.3390/ijms21207728.

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

Kentaro Fujiwara  1 , Keitaro Koyama  2 , Atsushi B Tsuji  1 , Hiroko Iwanari  3 , Osamu Kusano-Arai  3 , Tatsuya Higashi  1 , Toshimitsu Momose  2 , Takao Hamakubo  3   4
Affiliations

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

Kentaro Fujiwara et al. Int J Mol Sci. .

Abstract

We previously reported that radioimmunotherapy (RIT) using 90Y-labeled anti-ROBO1 IgG (90Y-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 90Y-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 90Y-B5209B. Tumor volume, body weight, and blood cell counts were monitored. The pathological analysis was performed on day seven post injection of 90Y-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 90Y-B5209B, making it a promising therapeutic strategy for SCLC.

Keywords: ROBO1; cisplatin; combination therapy; radioimmunotherapy; small-cell lung cancer.

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Conflict of interest statement

The authors declare no conflicts of interest associated with this manuscript.

Figures

Figure 1
Figure 1
Therapeutic impact and adverse effects observed in distinct treatment groups. (a) Change in tumor volume of the control group; (b) Kaplan–Meier survival curves; (c) Change in body weight. Black represents the control group, green represents the cisplatin-only group, blue represents the radioimmunotherapy (RIT)-only group, and red represents the combination therapy group. * p < 0.05 (vs. control group), ** p < 0.01 (vs. control group).
Figure 2
Figure 2
Peripheral blood count trends across distinct treatment groups. (a) Change in white blood cell (WBC) count; (b) Change in red blood cell (RBC) count; (c) Change in platelet (PLT) count. Black represents the control group, green represents the cisplatin-only group, blue represents the RIT-only group, and red represents the combination treatment group. * p < 0.05 (vs. control group), ** p < 0.01 (vs. control group).
Figure 3
Figure 3
Tumor specimen histology across distinct treatment groups (400× magnification, scale bar: 100 µm). (a) Control group; (b) Cisplatin-only group; (c) RIT-only group; (d) Combination therapy group.
Figure 4
Figure 4
Day 7 organ specimen histopathology (400× magnification, scale bar: 100 μm).
Figure 5
Figure 5
Day seven TUNEL analysis across distinct treatment groups (400× magnification, scale bar: 100 µm). (a) Control, (b) Cisplatin-only, (c) RIT-only, and (d) Combination therapy groups with associated TUNEL indices (e). * p < 0.01 (vs. combination group).
Figure 6
Figure 6
Therapeutic study experimental schedule.
See this image and copyright information in PMC

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