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 - Report - MDSpire
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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
First-in-Human Compassionate Use of NK-92 Cells with a CD5 CAR for Fusariosis
Overview
This report details the first-in-human use of SRCD5CAR-NK-92 cells for treating multidrug-resistant fusariosis. The patient demonstrated improved antifungal activity without significant adverse effects, highlighting the potential of this therapy in severe fungal infections.
Background
Invasive fungal infections (IFI) pose a significant challenge, particularly in immunocompromised patients, due to the emergence of multidrug-resistant strains and limited treatment options. The WHO has identified several fungal pathogens, including Fusarium spp., as high-priority targets for new therapeutic strategies. Immune-based therapies, particularly those utilizing engineered NK cells, present a promising avenue for enhancing antifungal responses.
Data Highlights
SRCD5CAR-NK-92 cells exhibited superior antifungal activity compared to untransduced NK-92 cells, particularly against a multidrug-resistant Fusarium petroliphilum isolate. The patient received escalating doses of irradiated SRCD5CAR-NK-92 cells without significant adverse effects.
Key Findings
SRCD5CAR-NK-92 cells showed enhanced antifungal activity against MDR Fusarium isolates.
The patient received intravenous infusions at 2-5 day intervals.
No significant local or systemic adverse effects were reported during treatment.
This represents the first application of SRCD5CAR-NK-92 cells in a human subject with severe MDR IFI.
The patient ultimately succumbed to their underlying hematological malignancy, not the treatment.
Clinical Implications
The use of SRCD5CAR-NK-92 cells may provide a novel off-the-shelf therapeutic option for patients with multidrug-resistant fungal infections. Further studies are needed to evaluate the long-term efficacy and safety of this approach in larger patient populations.
Conclusion
The compassionate use of SRCD5CAR-NK-92 cells demonstrates potential as a safe and effective strategy for treating severe multidrug-resistant fungal infections, warranting further investigation.
by María Velasco-de-Andrés, Pedro Puerta-Alcalde, Jiri Eitler, Lydia Krutz, Mariana Chumbita, Marta Español-Rego, Cristina Català, Laura Carrillo-Serradell, Violeta Planells-Romeo, Lucía Aragón-Serrano, Andrea Vergara, Amanda Isabel Pérez-Valencia, Patricia Monzó-Gallo, Antonio Gallardo-Pizarro, María Teresa Cibeira, Alexandru Vlagea, José Luis Caro, Eduard Palou, María Suárez-Lledó, Alex Soriano, Gonzalo Calvo, Álvaro Urbano-Ispizua, Torsten Tonn, Carolina Garcia-Vidal, Francisco Lozano