Adult peripheral blood and umbilical cord blood NK cells are good sources for effective CAR therapy against CD19 positive leukemic cells

Abstract

Among hematological cancers, Acute Lymphoblastic Leukemia (ALL) and Chronic Lymphocytic Leukemia (CLL) are the most common leukemia in children and elderly people respectively. Some patients do not respond to chemotherapy treatments and it is necessary to complement it with immunotherapy-based treatments such as chimeric antigen receptor (CAR) therapy, which is one of the newest and more effective treatments against these cancers and B-cell lymphoma. Although complete remission results are promising, CAR T cell therapy presents still some risks for the patients, including cytokine release syndrome (CRS) and neurotoxicity. We proposed a different immune cell source for CAR therapy that might prevent these side effects while efficiently targeting malignant cells. NK cells from different sources are a promising vehicle for CAR therapy, as they do not cause graft versus host disease (GvHD) in allogenic therapies and they are prompt to attack cancer cells without prior sensitization. We studied the efficacy of NK cells from adult peripheral blood (AB) and umbilical cord blood (CB) against different target cells in order to determine the best source for CAR therapy. AB CAR-NK cells are slightly better at killing CD19 presenting target cells and CB NK cells are easier to stimulate and they have more stable number from donor to donor. We conclude that CAR-NK cells from both sources have their advantages to be an alternative and safer candidate for CAR therapy.

Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia

“…CAR NK cells have the advantage to be activated not only by the CAR target antigen, but also by NCRs, thus adding ADCC-mediated mechanisms to the CAR-mediated cell lysis. Due to the dysregulation of patient-derived NK cells, most studies addressing the efficacy of NK cells-based adoptive immunotherapy consisted in the transfer of ex vivo expanded allogeneic NK cells derived from healthy donors' peripheral blood, umbilical cord blood, or cell lines (277,278). Allogeneic NK cells can be safely used as effector cells since they do not require a full HLA-matching and they do not induce graftversus-host disease, while harboring strong graft-versusleukemia effects (279,280).…”

Natural killer cells in cancer biology and therapy

“…Meanwhile, CD16-IL15-CD3 TriKE can activate suppressed NK cells and induce NK cell-mediated control of MDS and AML [ 248 ]. The advantages of CAR-NK therapy are obvious, including higher possibility of recognizing tumors (including cytokines and apoptosis) and lower incidence of CRS compared with CAR-T (Table 3 ) [ 249 , 250 ]. In 2018, Enli Liu et al transduced cord blood-derived NK cells with a retroviral vector incorporating the genes for CAR-CD19, inducible caspase-9-based suicide gene (iC9) and IL-15, and demonstrated the efficacy and safety in cell lines and the murine model.…”

You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy

“…NK cells isolated from cord blood (CB) present another possible starting material for a CAR-NK product [82]. Between 15% and 30% of CB lymphocytes are NK cells, and although contradictory reports have been published, they are generally considered to be more naïve in phenotype and function compared to peripheral blood (PB) NK cells.…”