LAUSR

Simple Summary Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for high-risk hematologic malignancies. However, disease recurrence after allo-HSCT remains a critical issue, underlining the need to develop maintenance therapy. In this context, NK cell-based immunotherapies could enhance graft-versus-tumor effect without triggering graft-versus-host disease. In this prospective phase I clinical trial, we demonstrated the safety of donor-derived NK cell infusion as a prophylactic treatment after allo-HSCT for patients with hematological malignancies. This opens perspectives for future developments of NK cell based therapeutic strategies after allo-HSCT with low incidence of GVHD, representing an advantage over post-transplant T cell modulations that are commonly used in clinical routine. Abstract 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.