Figure 2.

Effective combination of chemotherapy with anti-CTLA-4 therapy for the inhibition of the growth of EMT-6/P tumours. (A) Murine EMT-6/P cells were implanted s.c. in female Balb/c mice. Therapies began when tumours were 50 mm³; the mice received control saline (i.p.; n=7), anti-CTLA-4 (n=6), bolus plus ldCTX (n=7), a single dose of gemcitabine (160 mg kg⁻¹; n=5), ldCTX (ldCTX; n=6), or the combination of anti-CTLA-4 plus ldCTX (n=6). One additional group received anti-CTLA-4 therapy as a first line treatment and then (when the tumours began to relapse around day 21) a second-line therapy consisting of gemcitabine (160 mg kg⁻¹ every 3 days, i.p.; n=6), starting on day 21. *P<0.05 vs control, ^#P<0.05 vs CTLA-4 then gem (mean values±s.d.). (B) Mouse weights, as a measure of toxicity of the different treatments. (C) Kaplan–Meier plot of event-free survival, where duration of event-free survival is defined as time to primary tumour progression beyond 1200 mm³ or >15% weight loss. *P<0.05 was taken as statistical indication of difference vs controls and between treated groups. Significant event-free survival was observed with anti-CTLA-4 therapy, and this benefit could be improved by the combination of anti-CTLA-4 therapy plus metronomic CTX, or by the sequential regimen using a first line of anti-CTLA-4 followed by gemcitabine chemotherapy on relapsing tumours.