Extended Data Fig. 3: AC484 induces CD8+ T cell- and NK cell-mediated tumour regression in a variety of syngeneic and metastatic mouse models.
From: The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity
a, Survival analysis of animals bearing B16, KPC, 4T1, and EMT-6 tumours and treated with AC484 (red), anti-PD-1 (blue), or no treatment (black). Significance values reported for NTX v. AC484 in each. b, Survival analysis of animals bearing CT26 tumours and treated with AC484 (red), anti-PD-1 (blue), AC484 and anti-PD-1 (purple) or no treatment (black). Significance value reported for NTX vs. anti-PD-1 and AC484. c, Tumour growth over time and survival analysis of MC38 tumours in untreated or AC484-treated (1, 3, or 10 mg/kg) animals. Significance values reported for NTX vs. AC484 (3 mg/kg) and NTX vs. AC484 (10 mg/kg). d, Representative images of 4T1 lung metastases visualized in 15% India ink (left) and lung metastasis counts (right) for AC484-treated (20 mg/kg or 60 mg/kg) and vehicle-treated mice (n = 11-12 animals per group) on day 29 post-challenge e, Tumour growth over time and survival analysis for MC38 tumour-bearing mice treated with 20 mg/kg or 40 mg/kg doses of AC484 (left). Naive mice and mice that cleared tumours (cured) were rechallenged with MC38 tumour cells 1 year later. Bar plot showing tumour volumes on day 12 after rechallenge (right). f, Tumour growth over time for control or Jak1-null KPC tumours ± AC484 (n = 5–10 animals per group, data are mean ± SEM) g, Tumour growth over time for GVAX-treated B16 tumours treated with either isotype antibody (n = 10), anti-CD8 (αCD8, n = 10) or anti-NK depleting antibody (αNK1.1, n = 10), and treated with AC484 (red) compared to an untreated control group (n = 10; black). h, Tumour growth over time and survival analysis for B2m-null B16 tumours treated with AC484 (red) or untreated (black). i, Tumour growth over time for B2m-null KPC tumours treated with anti-NK depleting antibody (n = 10) or no depletion (n = 10) and treated with AC484 (red) compared to an untreated control group (n = 10; black). j, 4T1 lung metastasis counts for mice treated with either anti-CD8, anti-NK depleting antibody, or no depleting antibody, and treated with AC484 (red) compared to untreated control groups (black) (n = 11–23 animals per group).
