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D. Stroopinsky et al.
cells was quantified by MHC class I pentamer analysis. Compared to single-agent treatment, vaccination in com- bination with anti-PD1/TIM3/RGMb monoclonal anti- body treatment resulted in a statistically significant 1.8- fold expansion of spleen-derived T cells recognizing murine survivin in spleen CD8+ T cells (Figure 3G and H). Consistent with the tumor specificity of this response, vaccination and checkpoint inhibition did not result in an increased frequency of cytomegalovirus-specific CD8+ T cells.
To assess whether combination therapy with the fusion vaccine and checkpoint inhibition induces a memory response consistent with durable protection, we next interrogated the T-cell repertoire in the peripheral blood from surviving animals at day 36 after AML challenge. Combination treatment with the fusion vaccine and anti- PD1/TIM3/RGMb monoclonal antibodies led to a statisti-
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cally significant increase in the number of CD4/CD44+/CD62L– memory T cells as compared to the numbers following single-agent treatments. Furthermore, there was a statistically significant decrease in CD4+CD25+FOXP3+ regulatory T cells after combination treatment compared to that after vaccination (Online Supplementary Figure S1).
Induction of robust anti-tumor immunity after combi- natorial treatment with the syngeneic DC/AML fusion vaccine and checkpoint blockade was reproduced in an immune-competent mutant IDH2 inducible primary AML model. Mice were challenged with 200,000 GFP+ leukemia cells inoculated via the tail vein and then treated with the syngeneic DC/AML fusion vaccine and/or anti- PD1/TIM3/RGMb monoclonal antibodies, as described above. Analysis of spleens harvested from animals treated with the fusion vaccine and checkpoint inhibitors demon-
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Figure 3. Legend on the next page.
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haematologica | 2021; 106(5)