Sting-Activating Cyclic Dinucleotide-Manganese Nanoparticles Evoke Robust Immunity Against Acute Myeloid Leukemia

Authors

Marisa E Aikins
Xiaoqi Sun
Hannah Dobson
Xingwu Zhou
Yao Xu
Yu Leo Lei
James J Moon

Publication Date

4-1-2024

Journal

Journal of Controlled Release

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.

Keywords

Mice, Adult, Animals, Humans, Manganese, Neoplasms, Leukemia, Myeloid, Acute, Antineoplastic Agents, T-Lymphocytes, Nanoparticles, Immunotherapy, Immunity, Innate

Comments

Supplementary Material

Data Availability Statement

PMID: 38492861

DOI

10.1016/j.jconrel.2024.03.022

PMID

38492861

PMCID

PMC11032129

PubMedCentral® Posted Date

April 2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes