Background:
Acute myeloid leukemia (AML) is a type of heterogenous malignant hematological disorder. Recently developed
immunotherapies such as
chimeric antigen receptor T cell (CAR-T) do not demonstrated promising therapeutic results due to the off-target effect. The Dendritic cell-cytotoxic T lymphocyte adoptive immunotherapy (DC-CTL) is one of the recently developed
immunotherapies. One of the reasons that DC-CTL does not work well in AML is the lack of
antigens with high binding affinity, high antigen presentation potency, and the specificity to AML cells. Methods: DAC was used to treat AML cells to find overexpressed CTAs upon DAC treatment. The overexpression was confirmed at both
mRNA and
protein level by realtime PCR and western blotting.
Peptides was designed by using the NetMHCpan database and EPIP based on the out-screened
protein sequences. The
peptides were then used to pulse DC-CTL coculture in vitro and tested the cytotoxicity of CTLs in vitro and their
cancer inhibition potency in vivo. Results: Two
cancer testis antigen (CTA)
proteins, MAGEA1 and hTERT, was up-regulated in DAC treated AML cells. DC cells pulsed by the
antigen peptides designed based on the sequence of these two
proteins demonstrated increased potency to stimulate CTL cells in terms of
cytokines secretion. These
cytokines included IFN-γ,
IL-6, and TNF-α. Moreover, enhanced in vitro cytotoxicity was found in CTL cells treated with
peptide pulsed DC cells. AML progress was inhibited by CTA
peptides pulsed DC-CTL in a mouse AML model. Conclusions: MAGEA1 and hTERT could possibly serve as specific
tumor antigens upon DAC treatment, providing potential targets for the development of
immunotherapies for AML in the future.