{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T05:31:04Z","timestamp":1792215064434,"version":"4.4.0"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Invasive fungal infections (IFI) remain a major therapeutic challenge due to limited antifungal options, emergence of multidrug-resistant (MDR) strains and high mortality rates. This has turned up the development of immune-based therapies to restore and\/or enhance anti-fungal immune responses into a clinical priority. This is in line with the recent demonstration that antifungal activity of primary (cord blood-derived) NK cells can be potentiated by endowing them with a CD5-based second-generation chimeric antigen receptor (SRCD5CAR) targeting \u03b2-glucans, a constitutive and broadly distributed component of fungal cell walls. Building on this, we aimed at exploring whether the reported constitutive antifungal activity of leukemia-derived NK-92 cells can also be potentiated by engineering them for further potential use as a homogeneous and ready-to-use source of allogeneic cells for adoptive transfer therapy in IFI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      NK-92 cells lentivirally transduced and selected for stable and high-level expression of the SRCD5CAR for further testing in in vitro fungal killing assays, as well as in an\n                      <jats:italic>in vivo<\/jats:italic>\n                      model of fungal infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SRCD5CAR-NK-92 cells showed superior antifungal activity than untransduced NK-92 cell counterparts. SRCD5CAR-NK-92 cells also exhibited superior activity against a MDR\n                      <jats:italic>Fusarium petroliphilum<\/jats:italic>\n                      isolate from a patient undergoing a hematological malignancy and devoid of alternative therapeutic options. Following compassionate use approval, the patient received escalating intravenous infusions of irradiated SRCD5CAR-NK-92 cells at 2-5 day intervals, without significant local or systemic adverse effects (e.g., cytokine storm or alloreactivity).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Despite the patient ultimately succumbed due to progression of the underlying hematological malignancy, this represents first-in-human use of SRCD5CAR-NK-92 cells in the context of a severe MDR IFI.  The results highlight its potential as a safe and off-the-shelf therapeutic strategy, while underscoring the need for further investigation on efficacy and long-term outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1772830","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:56:59Z","timestamp":1778219819000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Translational development and first-in-human compassionate infusion of NK-92 cells expressing a CD5-based chimeric antigen receptor (SRCD5CAR-NK-92) in a patient with multidrug-resistant fusariosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Mar\u00eda","family":"Velasco-de-Andr\u00e9s","sequence":"first","affiliation":[{"name":"Immunoreceptors del sistema innat i adaptatiu, Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)","place":["Barcelona, 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