Editors' ChoiceAcute Myeloid Leukemia

Encapsulating a leukemia vaccine

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Science Translational Medicine  28 Oct 2020:
Vol. 12, Issue 567, eabf2642
DOI: 10.1126/scitranslmed.abf2642

Abstract

A self-healing microcapsule loaded with leukemia-associated antigens, epitope peptides, and PD-1 antibody demonstrates sustained delivery of a leukemia vaccine.

One of the most frequent hematological malignancies in adults, acute myeloid leukemia (AML), arises from clonal transformation and accumulation of hematopoietic precursors in the bone marrow and peripheral blood. AML has a notoriously guarded prognosis with elevated relapse rates commonly associated with traditional treatments such as chemotherapy. Alternative approaches, including T cell–specific immunotherapy designed to elicit an immune response against tumor-specific or tumor-associated antigens, have recently been developed as potential treatment strategies for AML—yet even with repeated administration regimens, rapid clearance of the antigen has hindered efficacy.

Now, Xie et al. report degradable porous microspheres for sustained release of a leukemia vaccine containing an antigen associated with leukemia and an immune checkpoint inhibitor, anti–PD-1 monoclonal antibody. Microcapsule preparation techniques including infrared radiation for sealing of the superficial pores were refined to effectively encapsulate the therapeutic cargo in a microsphere primarily made of polylactic acid. In a mouse model, the authors demonstrated enhanced recruitment of antigen presenting cells (APCs) and augmented internalization of the leukemia-specific antigen by these APCs, confirming the pro-inflammatory effects induced by the exogenous microcapsules and gradual antigen release. Analogously, fluorescence studies confirmed sustained delivery of the PD-1 antibody in lymph nodes, leading to enhanced proliferation and activity of cytotoxic T cells by the down-regulation of PD-1/PD-L1 signaling vigorously mediating T cell anergy in AML among numerous other cancers. Through humanized cell line or patient-derived xenograft mouse models, the authors demonstrated the clinical value of their formulation by showing improved tumor suppression and therapeutic outcomes compared with groups receiving repeated standard injections of the free antigen and antibody.

Although the work is initially limited to the use of a prototypic leukemia-specific antigen, it paves the way toward the adoption of porous microspheres as alternative immunologic adjuvants that can be readily fabricated and administered for broader applications. The safety and clinical utility of this delivery system, and the use of materials that have previously received regulatory approval for predicate devices, coalesce into a favorable path to clinical translation for this leukemia vaccine.

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