Journal Article

DKFZ-2026-01231

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.

Velasco-de-Andrés, M. ; Puerta-Alcalde, P. ; Eitler, J.DKFZ* ; Krutz, L. ; Chumbita, M. ; Español-Rego, M. ; Català, C. ; Carrillo-Serradell, L. ; Planells-Romeo, V. ; Aragón-Serrano, L. ; Vergara, A. ; Pérez-Valencia, A. I. ; Monzó-Gallo, P. ; Gallardo-Pizarro, A. ; Cibeira, M. T. ; Vlagea, A. ; Caro, J. L. ; Palou, E. ; Suárez-Lledó, M. ; Soriano, A. ; Calvo, G. ; Urbano-Ispizua, Á. ; Tonn, T.DKFZ* ; Garcia-Vidal, C. ; Lozano, F.

2026
Frontiers Media Lausanne

Abstract: 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 β-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.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 in vivo model of fungal infection.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 Fusarium petroliphilum 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).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.

Keyword(s): Humans (MeSH) ; Receptors, Chimeric Antigen: genetics (MeSH) ; Receptors, Chimeric Antigen: immunology (MeSH) ; Receptors, Chimeric Antigen: metabolism (MeSH) ; Killer Cells, Natural: immunology (MeSH) ; Killer Cells, Natural: transplantation (MeSH) ; Killer Cells, Natural: metabolism (MeSH) ; Immunotherapy, Adoptive: methods (MeSH) ; Animals (MeSH) ; Fusariosis: therapy (MeSH) ; Fusariosis: immunology (MeSH) ; Compassionate Use Trials (MeSH) ; Mice (MeSH) ; Drug Resistance, Multiple (MeSH) ; Male (MeSH) ; CAR ; CD5 ; NK-92 cells ; adoptive cell therapy ; fusariosis ; multidrug-resistance ; Receptors, Chimeric Antigen

Note: #DKTKZFB9#

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2026

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Database coverage:
; ; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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