Extended Data Fig. 1: Immune checkpoint inhibitors (ICIs) do not increase the efficacy of ALK TKIs in ALK+ lung cancer mouse models.
From: ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer

(a) Kaplan-Meier curves showing overall survival of mice described in Fig. 1c. Log-rank test, n/s, not significant (N = 3 mice per group). (b) Kaplan-Meier curves showing overall survival of mice described in Fig. 1d. Log-rank test; n/s, not significant (N = 4 mice per group) (c, d, e) Quantification of volume change compared with baseline tumor volume (change from baseline, % ± SEM) in hEML4-ALK Tg mice treated with higher doses (crizotinib: 100 mg/kg DIE; lorlatinib 10 mg/kg DIE) of ALK inhibitors and ICIs at T0 (c), T4 (d), and T8 (e) (Rat IgG, N = 12; anti-PD-1, N = 8; anti-PD-L1, N = 8; Crizotinib + Rat IgG, N = 13; Crizotinib + anti-PD-1, N = 8; Crizotinib + anti-PD-L1, N = 7; Lorlatinib + Rat IgG, N = 14; Lorlatinib + anti-PD-1, N = 7; Lorlatinib + anti-PD-L1, N = 8 mice). P values were calculated using an ordinary one-way Anova. (f) Kaplan-Meier curves showing overall survival of hEML4-ALK Tg mice treated with higher doses of ALK inhibitors and ICIs. Log-rank test; P values not significant. (Rat IgG, N = 12; anti-PD-1, N = 12; anti-PD-L1, N = 12; Crizotinib + Rat IgG, N = 13; Crizotinib + anti-PD-1, N = 8; Crizotinib + anti-PD-L1, N = 7; Lorlatinib + Rat IgG, N = 14; Lorlatinib + anti-PD-1, N = 9; Lorlatinib + anti-PD-L1, N = 8 mice). (g) Schematic representation of ALK peptide screening. Mice were vaccinated with a DNA encompassing the cytoplasmic portion of ALK, as previously described29. A set of 21 synthetic long peptides (SLPs) encompassing the coding region of the ALK-DNA vaccine was synthesized. Peptides A/B were synthetized to cover the cytoplasmic portion of hALK protein that is not represented in the ALK-DNA vaccine. (h-j) Benchmarking MHC-I algorithms for peptide-binding affinity prediction. NetMHC4.0 showing peptide affinity (predicted IC50 values in nM) vs. NetMHCpan4.1 showing the rank of the elution ligand likelihood (%Rank_EL). Computational predictions of peptide binding to MHC-I of SLPA (h), SLP7 (i) and SLP20 and 21 (j). Each dot represents a peptide. Peptide sequences and their correspondent predicted MHC-I allele can be found in Supplementary Table 3. Peptides represented in red or green indicate the best binder candidates.