Reinvigoration of innate and adaptive immunity via therapeutic cellular vaccine for patients with AML

Strategies integrating activation of innate and adaptive immunity against cancer are desired. We established a novel platform, Wilms’ tumor antigen 1 (WT1)-expressing artificial adjuvant vector cells (aAVC-WT1), linking invariant natural killer T (iNKT)-mediated dendritic cell to immunity. Here, we report the first-in-human application aAVC-WT1 in nine patients with relapsed refractory acute myelogenous leukemia. No dose-limiting toxicities were observed, whereas iNKT and/or NK was observed all patients. Five experienced objective leukemic regression, which correlated WT1-specific responses. Paired single-cell RNA receptor (TCR) sequencing demonstrated effector CD8+ clones bone marrow. Some marrow underwent transition from pre-existing precursor exhausted functional or emerged as newly activated cells, some maintained long term. These demonstrate feasibility safety therapy capacity this platform activate both humans.