358 Development of an allogenic FAP CAR iNKT product to target tumor stroma and modulate the tumor microenvironment

Michelet, Xavier; Popis, Martyna; Boi, Shannon K.; Niedzielska, Magda; Masakayan, Reed; Sharoni, Efrat Altman; Ibbett, Paul; Wright, Deborah; Kalinowska, Barbara Barbara; Keith, Justin; Joshi, Bishnu P.; Rossi, Moira Pinzan; Smith, Rachel A.; Yigit, Burcu; Tonquèze, Olivier Le; Chantzoura, Eleni; Dijk, Marc van

doi:10.1136/jitc-2022-sitc2022.0358

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“…iNKT cells engineered to express various CARs in preclinical studies can enhance tumor killing as well as target tumor stroma, reduce tumor microenvironment immunosuppression and promote infiltration of tumor specific CD8 + T cells 40 , 41 . Our allogeneic native iNKT cell therapy, agenT-797, continues to advance in further Phase 1/2 clinical trials alone and in combination (with anti-PD-1 immunotherapy) in solid tumors (NCT05108623) and multiple myeloma (NCT04754100).…”

Section: Discussionmentioning

confidence: 99%

A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome

Hammond,

Purbhoo,

Kadel

et al. 2024

Nat Commun

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Invariant natural killer T (iNKT) cells, a unique T cell population, lend themselves for use as adoptive therapy due to diverse roles in orchestrating immune responses. Originally developed for use in cancer, agenT-797 is a donor-unrestricted allogeneic ex vivo expanded iNKT cell therapy. We conducted an open-label study in virally induced acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome-2 virus (trial registration NCT04582201). Here we show that agenT-797 rescues exhausted T cells and rapidly activates both innate and adaptive immunity. In 21 ventilated patients including 5 individuals receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO), there are no dose-limiting toxicities. We observe an anti-inflammatory systemic cytokine response and infused iNKT cells are persistent during follow-up, inducing only transient donor-specific antibodies. Clinical signals of associated survival and prevention of secondary infections are evident. Cellular therapy using off-the-shelf iNKT cells is safe, can be rapidly scaled and is associated with an anti-inflammatory response. The safety and therapeutic potential of iNKT cells across diseases including infections and cancer, warrants randomized-controlled trials.

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Section: Discussionmentioning

confidence: 99%