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. 2022 May 23;10(5):e004644. doi: 10.1136/jitc-2022-004644

Figure 5.

Figure 5

Prophylactic IDH1R132H peptide vaccine extends survival only when combined with class I peptide vaccine and IDH1R132H inhibition. (A) 9-week-old dTG mice received s.c. vaccinations with 100 µg of R132Hp emulsified in IFA and 20 µg intramuscular (i.m.) poly-ICLC on days 0 and 11. On day 21, mice were euthanized, and their spleens were harvested. IFNγ secretion by splenocytes stimulated ex vivo for 72 hours with peptide-pulsed syngeneic CD11b+ cells as indicated. Cells from three individual mice were plated in technical triplicates. Media only, no CD11b+ cells negative control. (B) Schematic representation of the treatment protocol for prophylactic vaccinations. 9–10 week-old dTG mice received s.c. vaccinations as described in (A) followed by an intracerebral challenge with dTG-IDH1R132H cells. After 7 days, tumor-bearing mice were randomized to receive daily oral administrations of 10 mg/kg AG-881 or vehicle control for up to 35 consecutive days. Kaplan-Meier curves demonstrate survival outcomes: Sham, Vehicle (n=4); Sham, AG-881 (n=6); R132Hp, Vehicle (n=6), R132Hp, AG-881 (n=6). (C) Diagram representing the retroviral vector used to transduce the dTG-IDH1R132H cells with HLA class I TAA epitopes derived from gp100, tyrosinase-related protein 2 (Trp2), and tyrosinase (Tyr). (D) Schematic representation of the treatment protocol. 7–10-week-old dTG mice received s.c. vaccinations with the class II R132Hp, peptides gp100209-217, Trp2180-188, Tyr368-376 (class I vacc), or PBS (Sham Vacc) emulsified in IFA and 20 µg i.m. poly-ICLC. Vaccines were boosted 10 and 15 days later. And 21 days after initial vaccine administration, all mice received an intracerebral challenge with the dTG-IDH1R132H; Class I TAA+ cells tumor cells (described in (C)). Seven days later, tumor-bearing mice started receiving daily oral administration of 10 mg/kg AG-881 or vehicle control for up to 35 days. Kaplan-Meier curves demonstrate survival outcomes: Sham, Vehicle (n=4); Class I Vacc, Vehicle (n=4); R132Hp, AG-−881 (n=5), Class I Vacc, AG881 (n=5), and Class I+R132 Hp, AG-881 (n=5). *P<0.05; long-rank test. dTG, double transgenic; HLA, human leukocyte antigens; IFA, incomplete Freund adjuvant; TAA, tumor-associated antigen.