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Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membrane-decorated nanoparticles. | LitMetric

AI Article Synopsis

  • * Researchers developed a nanoparticle (LMN) made with macrophage membranes that can recognize cancer cells and deliver the drug LCL161, triggering an immune response by releasing certain proteins and cytokines from the tumor.
  • * The LMNs not only boost antitumor immunity by significantly increasing specific immune cell densities but also inhibit tumor growth in MHC-I-deficient TNBC and enhance survival rates in animal models, highlighting a new approach for treating hard-to-target cancers.

Article Abstract

Current cytotoxic T lymphocyte (CTL) activating immunotherapy requires a major histocompatibility complex I (MHC-I)-mediated presentation of tumor-associated antigens, which malfunctions in around half of patients with triple-negative breast cancer (TNBC). Here, we create a LCL161-loaded macrophage membrane decorated nanoparticle (LMN) for immunotherapy of MHC-I-deficient TNBC. SIRP on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161, which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer cells. The released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 folds. LMNs also block CD47-mediated phagocytosis suppression. LMNs inhibit the growth of MHC-I-deficient TNBC tumors, as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel, and prolong the survival of animals, during which process CTLs also play important roles. This macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophage-mediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252456PMC
http://dx.doi.org/10.1016/j.apsb.2024.04.009DOI Listing

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