G-Rex® for NK Cell Therapy

The simplest way to assemble quality NK cell therapies.

From donor-derived NK cells to iPSC-derived and genetically engineered CAR-NK therapies, G-Rex® provides a simple, scalable manufacturing foundation that can support your process from early development through clinical manufacturing.

The Value of Simplicity

In NK cell therapy, simplicity is the ultimate sophistication.

NK cell manufacturing can involve a wide range of starting materials, engineering strategies, activation methods, media, cytokines, and expansion approaches. G-Rex® provides a simple, flexible manufacturing foundation that can support those differences without making the culture system itself another source of unnecessary complexity.

From early research and preclinical development through large-scale clinical manufacturing, the same underlying G-Rex® technology can be used across formats to help maintain process continuity as requirements evolve.

Simplified Expansion

G-Rex® is well documented to facilitate robust expansion of NK cells from a variety of starting materials including peripheral blood, cord blood, and induced pluripotent stem cells.

Versatile & Flexible

Whether using feeder cells, feeder-free approaches, or engineered CAR constructs, G-Rex® has supported NK cell expansion across diverse manufacturing strategies

Scale with Continuity

Your same core process (on a per cm²) can be replicated across different log scales while maintaining continuity in your process and your drug product. This enables you to oscillate freely between small-scale G-Rex® well plates and large clinical scale G-Rex® bioreactors for time- and cost-efficient development and process improvement.

The Gold Standard

The gold standard for NK cell therapy.

For more than a decade, G-Rex® has evolved alongside NK cell therapy. Across donor-derived, cord blood-derived, iPSC-derived, genetically engineered, and CAR-NK approaches, academic researchers and industry developers have repeatedly incorporated G-Rex® as their programs move from discovery into process development, GMP, and clinical manufacturing.

Published workflows now span peripheral blood, cord blood, and iPSC-derived NK cells; feeder-based and feeder-free processes; viral and non-viral engineering; and both open and closed G-Rex® formats. G-Rex®-manufactured NK cell products have also progressed into Phase I clinical use.

As the field continues to diversify, G-Rex® provides a common manufacturing foundation across an increasingly broad range of NK cell therapy approaches.

G-Rex

Baylor College of Medicine

MD Anderson Cancer Center

Texas Children's Hospital

Case Western Reserve

Nationwide Children’s

University of Minnesota

Cross Cancer Institute

Fate Therapeutics

Fred Hutch

Indapta Therapeutics

National Cancer Institute

Purdue University

Rutgers Cancer Institute

Senti Bio

U.S. FDA — Center for Biologics

Fraunhofer IZI

ONK Therapeutics

Universitätsklinikum Carl Gustav Carus Dresden

Explore the Evidence →

A Typical Process

Assemble the NK cell manufacturing process that works for you.

There is no single way to make an NK cell therapy. Starting material, activation strategy, engineering method, and manufacturing scale can all vary. Explore how G-Rex® can fit into the process that works for your NK cell therapy.

Starting Material

Engineering

Viral OR Non-viral

  1. 01Peripheral Blood / Apheresis
  2. 02Isolation / Enrichment
  3. 03Activation
  4. 04Expansion
  5. 05Harvest & Concentration
  6. 06Formulation

Expansion

G-Rex®100M G-Rex®500M Two stacked CO2 incubators, the lower one open and loaded with G-Rex bioreactors Initial expansion to ~3-4 billion* cells Split and reseed Thermo Fisher Scientific CultiMaxx shelving configured for up to 10 G-Rex®500M-CS bioreactors. * Expansion numbers are a representative manufacturing example. Validate final published numbers with ScaleReady/CellReady SMEs before launch.
Can occur in G-Rex® Occurs outside G-Rex®

Recommended Products

Build your NK cell manufacturing process with ScaleReady.

ScaleReady brings together G-Rex® manufacturing technology with Bio-Techne media, cytokines, and gene-engineering tools to support NK cell process development from research through clinical manufacturing.

Next Steps

Whatever phase your NK cell program is at, a G-Rex® Optimization Specialist can help.

Whether you are developing a new NK cell process, transitioning an existing workflow into G-Rex®, optimizing a current G-Rex® process, or preparing to scale manufacturing, our team can help identify the path forward.

Frequently Asked Questions

Frequently asked questions about G-Rex® for NK cell therapy.

Can G-Rex® support clinical- and commercial-scale production of NK cells?

Absolutely. Clinical-scale NK manufacturing in G-Rex® is already well established. Published workflows have produced tens of billions of NK cells under GMP conditions, and G-Rex®-manufactured NK cell products have been administered to patients in clinical studies. G-Rex® has also been incorporated into GMP CAR-NK manufacturing workflows for clinical trials.

For commercial-scale production, G-Rex® supports both scale-up and scale-out, allowing manufacturing capacity to increase without fundamentally changing the underlying process. Published studies have demonstrated comparable NK and CAR-NK performance as processes moved from smaller G-Rex® formats into larger closed G-Rex® bioreactors.

Commercial-scale NK manufacturing has not yet been demonstrated through an approved NK-cell therapy because the field itself has not yet reached that stage of commercialization. That is a maturity-of-the-modality limitation - not an identified limitation of G-Rex®.

Sources: Otegbeye et al. (2022); Liu et al. (2021); Wang et al. (2024).

Are NK cell processes linearly scalable in G-Rex®?

Yes. Published NK-cell workflows have demonstrated process continuity across G-Rex® formats. Lapteva et al. reported that NK-cell fold expansion was the same in small G-Rex®10 and larger G-Rex®100 cultures when the process was run using the same underlying conditions. Liu et al. later described adapting a G-Rex® M100 process from preclinical protocols to linearly scale CAR-NK manufacturing to the desired GMP yield, and Wang et al. demonstrated comparable NK expansion, purity, phenotype, and function across G-Rex® multi-well plates and larger G-Rex®100M open- and closed-system bioreactors.

Linear scalability is one of the core advantages of the G-Rex® platform: capacity can increase while preserving the underlying culture architecture rather than requiring the process to be re-engineered around a different expansion technology.

Sources: Lapteva et al. (2016); Liu et al. (2021); Wang et al. (2024).

What are the advantages of scaling out across multiple G-Rex® bioreactors?

Scale-out provides a modular approach to manufacturing capacity. Developers can add or remove G-Rex® bioreactors as production requirements change rather than designing the entire process around a single maximum batch size. Distributing expansion across multiple vessels can also limit the consequence of an event isolated to one culture rather than concentrating the entire expansion in a single vessel.

Can G-Rex® support both donor-derived and iPSC-derived NK cells?

Yes. Published G-Rex® workflows include NK cells derived from peripheral blood and apheresis products, cord blood, and iPSCs. This gives developers flexibility to use the same underlying G-Rex® manufacturing technology across very different NK-cell sources.

Sources: Lapteva et al. (2012); Liu et al. (2021); Lupo et al. (2021).

Can G-Rex® support engineered NK and CAR-NK therapies?

Yes. G-Rex® has been incorporated into NK manufacturing workflows using viral CAR engineering, non-viral engineering, gene editing, armored CAR-NK cells, and engineered iPSC-derived NK cells. Depending on the workflow, the engineering step itself may occur outside G-Rex® before the engineered cells return to G-Rex® for continued expansion.

Sources: Lapteva et al. (2016); Liu et al. (2021); Wood et al. (2022); Wang et al. (2024); Lupo et al. (2024); Robbins et al. (2026).

Does NK cell manufacturing in G-Rex® require feeder cells?

No. G-Rex® can support both feeder-based and feeder-free NK manufacturing strategies. Recent peer-reviewed CAR-NK studies have demonstrated feeder-free manufacturing approaches using G-Rex®, while a substantial body of earlier NK literature demonstrates feeder-based processes.

Sources: Khanal et al. (2025); Khanal & Bhattarai (2025); Ruppel et al. (2026).

Can G-Rex® support feeder cell and or feeder-free NK culture?

Yes. G-Rex® has been used successfully with both feeder-dependent and feeder-free NK cell manufacturing strategies. On the feeder cell side, K562-based and membrane-bound IL-21 feeder systems have both been demonstrated in G-Rex®, achieving robust NK cell expansion from peripheral blood with yields suitable for clinical use.

For feeder-free approaches, G-Rex® has supported expansion of cord blood–derived CAR-NK cells, iPSC-derived NK cells, and CAR-NK cells using cytokine-based or engineered antigen-presenting cell conditions, all while retaining comparable phenotype, cytotoxicity, and post-thaw function to small-scale cultures. Across both strategies, the G-Rex® culture environment remains consistent. The platform accommodates your manufacturing approach, not the other way around.

Sources: Lapteva et al. (2016); Ojo et al. (2019); Liu et al. (2021); Lupo et al. (2024); Robbins et al. (2026); Wang et al. (2024).

What parts of an NK cell manufacturing process can be performed in G-Rex®?

That depends on the process. G-Rex® can provide a manufacturing environment for multiple stages of NK-cell development and production, including activation and expansion, with published workflows demonstrating different configurations. Some engineered NK processes perform gene transfer outside G-Rex® and return the cells to G-Rex® for subsequent expansion, while other unit operations may be incorporated depending on the process design.

Sources: Lapteva et al. (2016); Liu et al. (2021); Wang et al. (2024).

Have a different question? Connect with a G-Rex® Optimization Specialist.

Evidence & References

Peer-reviewed evidence from academia and industry.

Explore the published evidence supporting the use of G-Rex across NK cell research, development, and clinical manufacturing.

  1. Lapteva, N., et al. (2012). Large-scale ex vivo expansion and characterization of natural killer cells for clinical applications. Cytotherapy, 14, 1131-1143. https://doi.org/10.3109/14653249.2012.700767
  2. Shah, N., et al. (2013). Antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity. PLOS ONE, 8(10), e76781. https://doi.org/10.1371/journal.pone.0076781
  3. Lapteva, N., Szmania, S. M., van Rhee, F., & Rooney, C. M. (2014). Clinical grade purification and expansion of natural killer cells. Critical Reviews in Oncogenesis, 19(1-2), 121-132.
  4. Lapteva, N., Parihar, R., Rollins, L. A., Gee, A. P., & Rooney, C. M. (2016). Large-scale culture and genetic modification of human natural killer cells for cellular therapy. In Natural Killer Cells: Methods and Protocols (Methods in Molecular Biology, Vol. 1441, pp. 195-202). Springer. https://doi.org/10.1007/978-1-4939-3684-7_16
  5. Ojo, E. O., et al. (2019). Membrane bound IL-21 based NK cell feeder cells drive robust expansion and metabolic activation of NK cells. Scientific Reports, 9, 14916. https://doi.org/10.1038/s41598-019-51287-6
  6. Yang, Y., et al. (2020). Superior expansion and cytotoxicity of human primary NK and CAR-NK cells from various sources via enriched metabolic pathways. Molecular Therapy: Methods & Clinical Development, 18, 428-445. https://doi.org/10.1016/j.omtm.2020.06.014
  7. Liu, E., et al. (2021). GMP-compliant universal antigen presenting cells (uAPC) promote the metabolic fitness and antitumor activity of armored cord blood CAR-NK cells. Frontiers in Immunology, 12, 626098. https://doi.org/10.3389/fimmu.2021.626098
  8. Lupo, K. B., Moon, J.-I., Chambers, A. M., & Matosevic, S. (2021). Differentiation of natural killer cells from induced pluripotent stem cells under defined, serum- and feeder-free conditions. Cytotherapy, 23, 939-952. https://doi.org/10.1016/j.jcyt.2021.05.001
  9. Otegbeye, F., et al. (2022). A Phase I study to determine the maximum tolerated dose of ex vivo expanded natural killer cells derived from unrelated, HLA-disparate adult donors. Transplantation and Cellular Therapy, 28(5), 250.e1-250.e8. https://doi.org/10.1016/j.jtct.2022.02.008
  10. Wood, T., Bakir, A., Blanco, C., Iyer, D., Gorman, W., Lakshmireddy, H., Vilchez Juang, C., Nguyen, D., Giedlin, M., & Lee, P. (2022). Process development and scale-up for gene circuit engineered CAR-NK cell manufacturing [Conference poster/presentation]. ISCT Annual Meeting / Senti Biosciences.
  11. Brophy, S., et al. / O’Dwyer, M. (2022). CB derived, optimized affinity CD38 CAR-NK cells with CD38 KO show promising in-vivo activity in a Multiple Myeloma model [Poster]. ONK Therapeutics / Bio-Techne.
  12. Becker, A., Michen, S., Murad, S., Schackert, G., Eyüpoglu, I., & Temme, A. (2023). Development of large-scale expansion protocol for NKG2C-positive NK cells for treatment of glioblastoma [Poster].
  13. Wang, X., Byrne, M. E., Liu, C., Ma, M. T., & Liu, D. (2024). Scalable process development of NK and CAR-NK expansion in a closed bioreactor. Frontiers in Immunology, 15, 1412378. https://doi.org/10.3389/fimmu.2024.1412378
  14. Lupo, K. B., et al. (2024). synNotch-programmed iPSC-derived NK cells usurp TIGIT and CD73 activities for glioblastoma therapy. Nature Communications, 15, 1909. https://doi.org/10.1038/s41467-024-46343-3
  15. Khanal, S., Baer, A., & Bhattarai, N. (2025). Feeder cell-free production of CAR-NK cells via activation of PKC and calcium signaling pathways. Cytotherapy, 27, 1013-1022. https://doi.org/10.1016/j.jcyt.2025.05.008
  16. Khanal, S., & Bhattarai, N. (2025). A scalable protocol for ex vivo production of CAR-engineered human NK cells. Methods and Protocols, 8, 102. https://doi.org/10.3390/mps8050102
  17. Yin, C., Hamie, A., Kozuska, J., Debes-Marun, C., Tan, B., Tailor, P., & Chu, M. (2025). Pre-clinical characterization and process development of a BCMA-directed CAR NK-cell therapy product for relapsed/refractory multiple myeloma. Blood, 146(Suppl. 1), 7650. https://doi.org/10.1182/blood-2025-7650
  18. Ruppel, K. E., et al. (2026). Preclinical evaluation of a novel CD4 specific CAR NK cell therapy for T-cell malignancies. Cytotherapy, 28, 102140. https://doi.org/10.1016/j.jcyt.2026.102140
  19. Robbins, G. M., et al. (2026). Non-viral TcBuster transposon engineering of CD70-CAR natural killer cells for the treatment of osteosarcoma. Molecular Therapy: Oncology, 34, 201119. https://doi.org/10.1016/j.omton.2025.201119
  20. Thermo Fisher Scientific. (2023). CultiMaxx system for G-Rex bioreactors [Brochure]. Documents maximum capacity of 10 G-Rex500M-CS bioreactors per compatible Forma Steri-Cycle i250 / Heracell VIOS 250i CO2 incubator. https://documents.thermofisher.com/TFS-Assets/LPD/brochures/cultimaxx-steri-cycle-brochure.pdf
  21. Bigley, A. (2026). Harnessing the Power of g-NK Cells for Cancer and Autoimmune Disease [G-Rex Grant Tour presentation, Houston]. Indapta Therapeutics / ScaleReady. Vimeo: https://vimeo.com/1164462651
  22. Fate Therapeutics. Company presentation/video describing the iPSC-derived NK manufacturing platform; G-Rex shown in the NK expansion/manufacturing workflow. YouTube: https://www.youtube.com/watch?v=utFmI0S1mMA&t=425s