Current treatments for acute myeloid leukemia (AML) remain challenging, characterized by poor clinical outcomes. Exosomes, cell-derived membranous vesicles, has been emerging as a new modality of therapy. Here we designed and generated genetically reprogrammed exosomes with surface displayed antibodies and immunoregulatory proteins, namely programmed immune-engaging exosomes (PRIME Exos). By simultaneously targeting T cells and AML cells expressing C-type lectin-like molecule-1 (CLL-1), PRIME Exos can elicit tumor-specific immune responses and sustain cellular immunity against AML through modulating programmed death 1 (PD-1)- and CD27-mediated immune checkpoint pathways. In preclinical models of AML, PRIME Exos are demonstrated with promising efficacy and safety for suppressing leukemia expansion. This study developed a new exosome-based approach for AML immunotherapy.
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| http://dx.doi.org/10.1016/j.ymthe.2025.01.025 | DOI Listing |
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