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Intermittent chemotherapy can retain the therapeutic potential of anti-CD137 antibody during the late tumor-bearing state.

Tongu M, Harashima N, Tamada K, Chen L, Harada M - Cancer Sci. (2014)

Bottom Line: Although a significant antitumor effect was observed when local anti-CD137 mAb therapy (5 μg) was started early in the tumor-bearing stage (day 10), no therapeutic efficacy was observed when the mAb therapy was started at a later tumor-bearing stage (day 17).In a bilateral tumor inoculation model, this combination therapy achieved systemic therapeutic effects and suppressed the growth of mAb-untreated tumors.These results suggest that intermittent immunochemotherapy using CP and GEM could retain the therapeutic potential of anti-CD137 mAb that is normally impaired during the late tumor-bearing stage.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Animals, Center for Integrated Research in Science, Shimane University, Izumo, Japan.

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Systemic antitumor effects of combination therapy. (a) BALB/c mice were injected s.c. and bilaterally with CT26 (right flank, 5 × 105 cells; left flank, 2.5 × 105 cells). CP (50 mg/kg) and GEM (50 mg/kg) were injected i.p. on days 10 and 18. Subsequently, anti-CD137 mAb (5 μg) or rat IgG was injected i.t. into the CT26 tumor on the right flank on days 19, 21 and 23. White arrows indicate the injection of CP and GEM, and black arrows indicate the local injections of Ab. Tumor size (mm2) was measured twice weekly. There were 11 mice in the control group, and 12 mice in the treatment group. (b) The statistical significance of tumor size was evaluated on day 30 after tumor inoculation. *P < 0.05, **P < 0.01 (anova with Bartlett's test) N.S., not significant.
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fig05: Systemic antitumor effects of combination therapy. (a) BALB/c mice were injected s.c. and bilaterally with CT26 (right flank, 5 × 105 cells; left flank, 2.5 × 105 cells). CP (50 mg/kg) and GEM (50 mg/kg) were injected i.p. on days 10 and 18. Subsequently, anti-CD137 mAb (5 μg) or rat IgG was injected i.t. into the CT26 tumor on the right flank on days 19, 21 and 23. White arrows indicate the injection of CP and GEM, and black arrows indicate the local injections of Ab. Tumor size (mm2) was measured twice weekly. There were 11 mice in the control group, and 12 mice in the treatment group. (b) The statistical significance of tumor size was evaluated on day 30 after tumor inoculation. *P < 0.05, **P < 0.01 (anova with Bartlett's test) N.S., not significant.

Mentions: Finally, we assessed whether combination treatment with intermittent chemotherapy and anti-CD137 mAb exerted an antitumor effect on tumors not treated with mAb on the opposite flank of the mice. Mice were injected s.c. and bilaterally with CT26 cells, and anti-CD137 mAb therapy was administered locally to the right-side tumor (Fig.5a,b). Although there was no statistically significant tumor growth of the right-side tumors between the mice treated with chemotherapy and control Ab and those with chemotherapy with anti-CD137 mAb, the combination therapy suppressed the growth of mAb-untreated tumors significantly (Fig.5a,b). In addition, the tumor regression rate after combination therapy was significantly higher than that after the combination of chemotherapy and control Ab (Table1).


Intermittent chemotherapy can retain the therapeutic potential of anti-CD137 antibody during the late tumor-bearing state.

Tongu M, Harashima N, Tamada K, Chen L, Harada M - Cancer Sci. (2014)

Systemic antitumor effects of combination therapy. (a) BALB/c mice were injected s.c. and bilaterally with CT26 (right flank, 5 × 105 cells; left flank, 2.5 × 105 cells). CP (50 mg/kg) and GEM (50 mg/kg) were injected i.p. on days 10 and 18. Subsequently, anti-CD137 mAb (5 μg) or rat IgG was injected i.t. into the CT26 tumor on the right flank on days 19, 21 and 23. White arrows indicate the injection of CP and GEM, and black arrows indicate the local injections of Ab. Tumor size (mm2) was measured twice weekly. There were 11 mice in the control group, and 12 mice in the treatment group. (b) The statistical significance of tumor size was evaluated on day 30 after tumor inoculation. *P < 0.05, **P < 0.01 (anova with Bartlett's test) N.S., not significant.
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fig05: Systemic antitumor effects of combination therapy. (a) BALB/c mice were injected s.c. and bilaterally with CT26 (right flank, 5 × 105 cells; left flank, 2.5 × 105 cells). CP (50 mg/kg) and GEM (50 mg/kg) were injected i.p. on days 10 and 18. Subsequently, anti-CD137 mAb (5 μg) or rat IgG was injected i.t. into the CT26 tumor on the right flank on days 19, 21 and 23. White arrows indicate the injection of CP and GEM, and black arrows indicate the local injections of Ab. Tumor size (mm2) was measured twice weekly. There were 11 mice in the control group, and 12 mice in the treatment group. (b) The statistical significance of tumor size was evaluated on day 30 after tumor inoculation. *P < 0.05, **P < 0.01 (anova with Bartlett's test) N.S., not significant.
Mentions: Finally, we assessed whether combination treatment with intermittent chemotherapy and anti-CD137 mAb exerted an antitumor effect on tumors not treated with mAb on the opposite flank of the mice. Mice were injected s.c. and bilaterally with CT26 cells, and anti-CD137 mAb therapy was administered locally to the right-side tumor (Fig.5a,b). Although there was no statistically significant tumor growth of the right-side tumors between the mice treated with chemotherapy and control Ab and those with chemotherapy with anti-CD137 mAb, the combination therapy suppressed the growth of mAb-untreated tumors significantly (Fig.5a,b). In addition, the tumor regression rate after combination therapy was significantly higher than that after the combination of chemotherapy and control Ab (Table1).

Bottom Line: Although a significant antitumor effect was observed when local anti-CD137 mAb therapy (5 μg) was started early in the tumor-bearing stage (day 10), no therapeutic efficacy was observed when the mAb therapy was started at a later tumor-bearing stage (day 17).In a bilateral tumor inoculation model, this combination therapy achieved systemic therapeutic effects and suppressed the growth of mAb-untreated tumors.These results suggest that intermittent immunochemotherapy using CP and GEM could retain the therapeutic potential of anti-CD137 mAb that is normally impaired during the late tumor-bearing stage.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Animals, Center for Integrated Research in Science, Shimane University, Izumo, Japan.

Show MeSH
Related in: MedlinePlus