Natural killer cells for immunotherapy

  • Versatile – customized strategies for manufacturing of NK cell products
  • Convenient – CliniMACS® System in combination with MACS® GMP products
  • Promising – Anti-tumor and -infection responses reported in numerous publications

Your research matters.  We know the challenges and hurdles. That is why Miltenyi Biotec is committed to go with you every step of your ground-breaking research. Together, we work towards translating your findings into the clinic, quicker and easier with our wide variety of research, premium and GMP products.

Automated manufacturing of CAR NK cells

Join Martha Elia Luevano Salinas, Ph.D. and her webinar on the automated manufacturing of CAR NK cells, providing some background information, strategies and means for CAR NK cell manufacturing.

Scientific poster
Developing a GMP-compliant, automated process to generate CAR NK cells in a closed system for clinical use

Sabine Müller, Melanie Sohmen, Julia Kostyra, Angela Mekes, Congcong Zhang, Ra jul Bari, Wing Leung, and Nina Möker

NK MACS Medium and NK MACS GMP Medium have been optimized for the cultivation, activation and expansion of isolated human NK cells or NK cells from peripheral blood mononuclear cells (PBMCs). It is manufactured without animal-derived components and is fully translational.

  • Superior NK cell expansion*
  • Xeno-free
  • Minimal growth of unwanted cells like B-, T-, and DC cells

*Supplementation with serum or autologous plasma is necessary

NK cell expansion using NK MACS Medium (research use) and NK MACS GMP Medium
NK cell expansion using NK MACS Medium (research use) and NK MACS GMP Medium (Phenol Red)

NK cell fold expansion from PBMCs (n=3) using 5% AB serum and 500 IU/mL of IL-2 and 140 U/mL IL-15 during 14 days showed high fold expansion rates for both, NK MACS Medium (light purple circle) and NK MACS GMP Medium (Phenol Red) (dark purple square).

Natural killer (NK) cells play a major role in immune surveillance and in the early immune response to cancer and infections¹,². Beneficial anti-tumor responses have been observed, illustrating the safety profile and clinical potential of this treatment³,⁴. With an increasing availability of anti-cancer drugs, the role of NK cell-based approaches in novel combination therapies has rapidly escalated⁵,⁶.

The use of specific CliniMACS® Product Lines allows GMP-compliant manufacturing of NK cell products according to the needs given by a specific treatment concept.

Highly enriched NK cell products are generated by CD3 depletion followed by CD56 enrichment. A combined NK cell and natural killer T (NKT) cell product is produced by a single CD56 enrichment step. Heterogeneous NK cell products can be manufactured by either CD3 or TCRα/β depletion, optionally in combination with CD19 depletion is B cell depletion is required.

The latter two manufacturing strategies for NK cells allow co-enrichment of NK cells and accessory cells, such as monocytes and dendritic cells (CDs). In case of TCRα/β depletion γ/δ T cells are also preserved within the NK cell product.

Application note
Depletion of CD3+ and/or enrichment of CD56+ cells

Take a look at workflows for the magnetic depletion of CD3+ cells, the magnetic enrichment of CD56+ cells from leukapheresis and the magnetic enrichment of CD56+ cells from CD3+ pre-depleted leukapheresis.

  1. Chiossone, L. et al. (2018) Natural killer cells and other innate lymphoid cells in cancer. Nat. Rev. Immunol. 18: 671–688.
  2. Hammer, Q. et al. (2018) Natural killer cell specificity for viral infections. Nat. Immunol. 19: 800-808.
  3. Miller, J. S. et al. (2005) Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105: 3051–3057.
  4. Curti, A. et al. (2011) Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood 118: 3273–3279.
  5. Bachanova, V. et al. (2018) Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells. Immunother. 67: 483-94.
  6. Talleur, A. C. et al. (2017) Consolidation Therapy for Newly Diagnosed Pediatric Patients with High-Risk Neuroblastoma Using Busulfan/Melphalan, Autologous Hematopoietic Cell Transplantation, Anti-GD2 Antibody, Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-2, and Haploidentical Natural Killer Cells. Biol. Blood Marrow Transplant. 23: 1910–1917.

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