Good manufacturing practices production of natural killer cells for immunotherapy: a six‐year single‐institution experience

Abstract

Clinical-scale production of NK cells is efficient and can be performed under GMPs. The purified NK cell product results in high NK cell purity with minimal contamination by T cells, monocytes, and B cells, but it requires more time for processing and results in a lower NK cell recovery when compared to NK cell enrichment with CD3 cell depletion alone. Additional laboratory studies and results from clinical trials will identify the best source and type of NK cell product.

T-cell and natural killer cell therapies for hematologic malignancies after hematopoietic stem cell transplantation: enhancing the graft-versus-leukemia effect

“…using magnetic depletion of CD3 + populations), followed by a further purification step for CD56 + populations 87,88 and/or subsequent enrichment with cytokines ( Figure 5). Mononuclear cells are subjected to immunomagnetic selection to remove unwanted CD3 + Tcell populations.…”

“…Although subsequent purification steps yielded higher purity, a substantially increased processing time (and consequent lower recovery) was needed. 87 Enrichment steps involve the cytokines IL-2, IL-15, or various feeder cells (K562 cells of myeloid lineage modified to express IL-15, 89 irradiated autologous peripheral blood mononuclear cells in the presence of IL-2, 90 or autologous mesenchymal stromal cells 91 ). Both IL-2 and IL-15 appear equally efficacious cytokines for expanding NK cells ex vivo and no added benefit was seen when both were combined or combined with other cytokines (e.g.…”

Combined IL-15 and IL-12 drives the generation of CD34+-derived natural killer cells with superior maturation and alloreactivity potential following adoptive transfer

“…8,9 Although infusions with peripheral blood derived-NK cells appears to be safe, NK cell enrichment from leukapheresis products yields relatively low NK cell numbers with contaminating alloreactive T cells. [11][12][13][14] To overcome these limitations, several methods have been explored to activate and expand NK cells before adoptive transfer. [15][16][17][18][19][20] Alternatively, NK cells can be generated from hematopoietic progenitor cells (HPCs).…”

Specific growth inhibition of ErbB2‑expressing human breast cancer cells by genetically modified NK‑92 cells

“…Natural killer (NK) cells are important effectors of the innate immune system and play an essential role in the body's first line of defense against virus-infected and malignant cells (1,2). NK cells rapidly recognize different pathogens through a variety of activation and inhibition receptors, and mediate spontaneous tumor cytotoxicity in a major histocompatibility complex (MHC)-unrestricted manner (3).…”