Expanded NK cells from umbilical cord blood and adult peripheral blood combined with daratumumab are effective against tumor cells from multiple myeloma patients

Oncoimmunology. 2020 Dec 29;10(1):1853314. doi: 10.1080/2162402X.2020.1853314.

Abstract

In this study we evaluated the potential of expanded NK cells (eNKs) from two sources combined with the mAbs daratumumab and pembrolizumab to target primary multiple myeloma (MM) cells ex vivo. In order to ascertain the best source of NK cells, we expanded and activated NK cells from peripheral blood (PB) of healthy adult donors and from umbilical cord blood (UCB). The resulting expanded NK (eNK) cells express CD16, necessary for carrying out antibody-dependent cellular cytotoxicity (ADCC). Cytotoxicity assays were performed on bone marrow aspirates of 18 MM patients and 4 patients with monoclonal gammopathy of undetermined significance (MGUS). Expression levels of PD-1 on eNKs and PD-L1 on MM and MGUS cells were also quantified. Results indicate that most eNKs obtained using our expansion protocol express a low percentage of PD-1+ cells. UCB eNKs were highly cytotoxic against MM cells and addition of daratumumab or pembrolizumab did not further increase their cytotoxicity. PB eNKs, while effective against MM cells, were significantly more cytotoxic when combined with daratumumab. In a minority of cases, eNK cells showed a detectable population of PD1+ cells. This correlated with low cytotoxic activity, particularly in UCB eNKs. Addition of pembrolizumab did not restore their activity. Results indicate that UCB eNKs are to be preferentially used against MM in the absence of daratumumab while PB eNKs have significant cytotoxic advantage when combined with this mAb.

Keywords: Multiple Myeloma; NK cells; PD-1; cell Therapy and Immunotherapy; cytotoxicity; daratumumab.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal / pharmacology
  • Fetal Blood
  • Humans
  • Killer Cells, Natural
  • Multiple Myeloma* / drug therapy

Substances

  • Antibodies, Monoclonal
  • daratumumab

Grants and funding

This work was supported by the PRT-K program 2018 [MV and GC; 2018-021] and Canceropole GSO Emergence [MV; 2018/2019]. This work was also supported by La Ligue Regionale contre le Cancer (GC), the “Investissements d’avenir” Grant LabEx MAbImprove: ANR-10-LABX-53 (GC/MV), the NK 001 project financed by the “Fond Européen de Développement Régional“ [FEDER-FSE-IEJ 2014/2020] and by “Région Occitanie Pyrénées-Méditerranée”, by grant [SAF2016-76338-R] from Ministerio de Economía y Competitividad (MINECO) to AA and by Gobierno de Aragón (Group) cofinanced by Feder 2014-2020 “Building Europe from Aragon”. CRO was supported by an EFIS short-term fellowship and DG by a predoctoral fellowship from Governement of Aragon.