Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters.

Sarah Parisi,Giovanni Martinelli,Elena Urbani,Antonio Curti,Loredana Ruggeri,Letizia Zannoni,Simonetta Rizzi,Gabriella Chirumbolo,Giovanni Marconi,Barbara Sinigaglia,Stefania Paolini,Chiara Sartor,Valeria Giudice,Andrea Bontadini,Gianluca Cristiano,Roberto M Lemoli,Sara Ciardelli,Andrea Velardi,Mario Arpinati,Cristina Papayannidis,Elisa Dan,Francesca Bonifazi,Russell E Lewis,Jacopo Nanni,Darina Očadlíková ,Michèle Cavo

doi:10.3389/fimmu.2021.804988

Abstract

Recently, many reports were published supporting the clinical use of adoptively transferred natural killer (NK) cells as a therapeutic tool against cancer, including acute myeloid leukemia (AML). Our group demonstrated promising clinical response using adoptive immunotherapy with donor-derived alloreactive KIR-ligand-mismatched NK cells in AML patients. Moreover, the antileukemic effect was correlated with the dose of infused alloreactive NK cells (“functional NK cell dose”). Herein, we update the results of our previous study on a cohort of adult AML patients (median age at enrollment 64) in first morphological complete remission (CR), not eligible for allogeneic stem cell transplantation. After an extended median follow-up of 55.5 months, 8/16 evaluable patients (50%) are still off-therapy and alive disease-free. Overall survival (OS) and disease-free survival (DFS) are related with the dose of infused alloreactive NK cells (≥2 × 105/kg).

Highlights

Natural killer (NK) cells are lymphocytes expressing CD56 or CD16 antigens on their surface and lacking CD3
The authors retrospectively demonstrated that the presence of killer cell immunoglobulin-like receptors” (KIRs)-L mismatch between donor and recipient was significantly related with a better response in preventing leukemia relapse
Haploidentical KIR-L-mismatched donors were selected if at least one allele mismatch at a class I locus among the following ones was present: HLA-C alleles with Asn77-Lys80, HLA-C alleles with Ser77-Asn80, and HLA-Bw4 alleles

Summary

Introduction

Natural killer (NK) cells are lymphocytes expressing CD56 or CD16 antigens on their surface and lacking CD3. Based on this seminal work, our group analyzed the results of adoptive immunotherapy with donor-derived highly purified KIR-ligand-mismatched, haploidentical NK cells in a cohort of relapsed or refractory, adult, high-risk, AML patients in a phase I study [7]. Among 16 patients evaluable for response, 9 were alive and disease-free after a median follow-up of 22.5 months (range, 6–68 months).

Results

Conclusion