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Fig. 3 | Journal for ImmunoTherapy of Cancer

Fig. 3

From: Targeting the TGFβ pathway with galunisertib, a TGFβRI small molecule inhibitor, promotes anti-tumor immunity leading to durable, complete responses, as monotherapy and in combination with checkpoint blockade

Fig. 3

Galunisertib monotherapy displays dose dependent activity against established orthotopic 4T1-LP tumors with immunologic memory and antigen spreading. a Mean and individual tumor growth curves for Balb/c mice injected orthotopically in the mammary fat pad with 4T1-LP tumor cells and treated with galunisertib (37.5, 75 or 150 mg/kg BID) when tumors reached ~ 300 mm3 (8 days after implantation). The number of CRs were: 1/10, 3/10 and 5/10 for mice treated with Galunisertib at 37.5 mg/kg, 75 mg/kg and 150 mg/kg, respectively. b Percent body weight change on average of mice treated with galunisertib at 37.5 mg/kg, 75 mg/kg and 150 mg/kg. c Frequencies and representative plots of CD3+ and NK T cells of total live CD45+ cells in in single cell suspensions prepared from tumors harvested after 8 days of galunisertib treatment. Tumors from 5 mice/group treated with 75 mg/kg galunisertib or vehicle control were analyzed. Student’s t-tests were used to evaluate statistical significance (ns: p ≥ 0.05). d Mice which had regressed 4T1-LP tumors after treatment with galunisertib (37.5, 75 or 150 mg/kg BID for 28 days; as shown in a) were rechallenged orthotopically with 4T1-LP in one mammary fat pad and received a primary challenge of a different triple negative breast cancer tumor, EMT6-LM2, in an alternate fat pad, at day 85 post the original 4T1-LP tumor challenge. Average tumor growth curves of secondary 4T1-LP and EMT-6-LM2 challenge are shown for each group. e Mice which had regressed 4T1-LP tumors after treatment with galunisertib (75 mg/kg BID for 28 days) were rechallenged orthotopically with the poorly immunogenic 4T1 parental tumor cells at day 85 post the original 4T1-LP tumor challenge. Average tumor growth curves of secondary 4T1-LP challenge are shown. Individual tumor growth curves of naïve mice injected orthotopically with 4T1 parental tumors are shown as a control. Data shown are representative of two independent experiments with 10–12 mice/group

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