1. STING-activating cyclic dinucleotide-manganese nanoparticles evoke robust immunity against acute myeloid leukemia.
- Author
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Aikins, Marisa E., Sun, Xiaoqi, Dobson, Hannah, Zhou, Xingwu, Xu, Yao, Lei, Yu Leo, and Moon, James J.
- Subjects
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ACUTE myeloid leukemia , *IMMUNOLOGIC memory , *TYPE I interferons , *IMMUNE checkpoint proteins , *INTERFERON receptors , *IMMUNITY , *CYTOTOXIC T lymphocyte-associated molecule-4 , *NANOPARTICLES - Abstract
Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults with a 5-year survival rate of 30.5%. These poor patient outcomes are attributed to tumor relapse, stemming from ineffective innate immune activation, T cell tolerance, and a lack of immunological memory. Thus, new strategies are needed to activate innate and effector immune cells and evoke long-term immunity against AML. One approach to address these issues is through Stimulator of Interferon Genes (STING) pathway activation, which produces Type I Interferons (Type I IFN) critical for innate and adaptive immune activation. Here, we report that systemic immunotherapy with a lipid-based nanoparticle platform (CMP) carrying Mn2+ and STING agonist c -di-AMP (CDA) exhibited robust anti-tumor efficacy in a mouse model of disseminated AML. Moreover, CMP immunotherapy combined with immune checkpoint blockade against cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) elicited robust innate and adaptive immune activation with enhanced cytotoxic potential against AML, leading to extended animal survival after re-challenge with AML. Overall, this CMP combination immunotherapy may be a promising approach against AML and other disseminated cancer. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2024
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