1. STING-activating cyclic dinucleotide-manganese nanoparticles evoke robust immunity against acute myeloid leukemia.
- Author
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Aikins ME, Sun X, Dobson H, Zhou X, Xu Y, Lei YL, and Moon JJ
- Subjects
- Mice, Adult, Animals, Humans, Manganese, T-Lymphocytes, Immunotherapy, Immunity, Innate, Neoplasms, Leukemia, Myeloid, Acute drug therapy, Antineoplastic Agents, 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 Mn
2+ 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., Competing Interests: Declaration of competing interest J.J.M. declares financial interests for board membership, as a paid consultant, for research funding, and/or as an equity holder in Saros Therapeutics and EVOQ Therapeutics. The University of Michigan has a financial interest in EVOQ Therapeutics. Y.L.L declares financial interests for board membership and/or as an equity holder in Saros Therapeutics. X.S. is an employee and shareholder in Editas Medicine., (Copyright © 2024 Elsevier B.V. All rights reserved.)- Published
- 2024
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