Phase I Trial of Prophylactic Donor-Derived IL-2-Activated NK Cell Infusion after Allogeneic Hematopoietic Stem Cell Transplantation from a Matched Sibling Donor

Raynier Devillier (1, 2) , Boris Calmels (2) , Sophie Guia (3) , Mohammed Taha , Cyril Fauriat (2) , Bechara Mfarrej (2) , Geoffroy Venton (3) , Eric Vivier (3, 4, 5) , Daniel Olive (2) , Christian Chabannon (2) , Didier Blaise (2) , Sophie Ugolini (3)

1 IPC - Institut Paoli-Calmettes
2 CRCM - Centre de Recherche en Cancérologie de Marseille
3 CIML - Centre d'Immunologie de Marseille - Luminy
4 Innate Pharma
5 TIMONE - Hôpital de la Timone [CHU - APHM]

Background: NK cell-based immunotherapy to prevent relapse after allogeneic transplantation is an appealing strategy because NK cells can provide strong antitumor effect without inducing graft-versus-host disease (GVHD). Thus, we designed a phase-I clinical trial evaluating the safety of a prophylactic donor-derived ex vivo IL-2 activated NK cell (IL-2 NK) infusion after allo-HSCT for patients with hematologic malignancies. Methods: Donor NK cells were purified and cultured ex vivo with IL-2 before infusion, at three dose levels. To identify the maximum tolerated dose was the main objective. In addition, we performed phenotypical and functional characterization of the NK cell therapy product, and longitudinal immune monitoring of NK cell phenotype in patients. Results: Compared to unstimulated NK cells, IL-2 NK cells expressed higher levels of activating receptors and exhibited increased degranulation and cytokine production in vitro. We treated 16 patients without observing any dose-limiting toxicity. At the last follow up, 11 out of 16 treated patients were alive in complete remission of hematologic malignancies without GVHD features and immunosuppressive treatment. Conclusions: Prophylactic donor-derived IL-2 NK cells after allo-HSCT is safe with low incidence of GVHD. Promising survivals and IL-2 NK cell activated phenotype may support a potential clinical efficacy of this strategy.

Mots clés: allogeneic hematopoietic stem cell transplantation; cellular immunotherapy; IL-2-activated NK cells; antitumor immunity

Domaines: Sciences du Vivant [q-bio]

Raynier Devillier, Boris Calmels, Sophie Guia, Mohammed Taha, Cyril Fauriat, et al.. Phase I Trial of Prophylactic Donor-Derived IL-2-Activated NK Cell Infusion after Allogeneic Hematopoietic Stem Cell Transplantation from a Matched Sibling Donor. Cancers, 2021, 13 (11), pp.2673. ⟨10.3390/cancers13112673⟩. ⟨hal-03374755⟩