Evaluating the safety and feasibility of allogeneic NK cell infusion in high-risk lymphoma patients post-autologous stem cell transplantation

Abstract

Lymphoma, a cancer with poor prognosis is a growing global health challenge that encompasses two primary types, Hodgkin (HL) and non-Hodgkin lymphoma (NHL), each further divided into various subtypes with distinct biological behaviors. Conventional therapeutic strategies include chemotherapy, radiation, surgery, and autologous hematopoietic stem cell transplantation (auto-HSCT). Natural killer (NK) cells exhibit intrinsic cytotoxicity against tumor cells without the need for prior immunization or activation. In this prospective clinical trial, we evaluated the feasibility of allogeneic NK cell therapy in patients with high-risk lymphoma who had a poor prognosis. Each patient received 1 × 107 NK cells/kg infusion without interleukin-2 (IL-2) supplementation. Therapy was tolerated without graft-versus-host-disease, cytokine release syndrome, or neurotoxicity. During the follow-up period, 7 had complete responses (CR) (87.5%) and one case exhibited stable disease (SD) (12.5%). In summary, our investigations support the development of allogeneic NK cellular therapies for advanced lymphoma to overcome chemoresistance. Therapeutic efficacy may be further improved by disrupting the immunosuppressive environment and infusion of exogenous IL-15. This approach presents a promising and pragmatic strategy for managing high-risk lymphoma post-HSCT. Future research should focus on optimizing NK cell dosages and infusion frequency to maximize treatment effectiveness.

Keywords: Cellular immunotherapy; Clinical trial; Immunotherapy; Lymphoma; Natural killer cells; Phase I.

Fig. 1

Expansion and functional characterization of NK Cells. a The frequency of CD56⁺CD3⁻ NK cells derived from peripheral blood mononuclear cells (PBMCs) exceeded 80% following magnetic-activated cell sorting (MACS). b Co-culturing of activated NK cells (E) and K562 cells (T) at different E: T ratios using LDH assay, indicated the most cytotoxic effect in 10:1 E: T. ratio c, d On day 21 post-activation, cytokine release was assessed, revealing mean concentrations of approximately 29.33 pg/mL for IFN-γ and 78.5 pg/mL TNF-α in NK cells co-cultured with K562 cell line, both significantly elevated compared to the control NK groups. All data are presented as means ± standard deviation (M ± SD, n = 3). **P ≤ 0.01, and ***P ≤ 0.001