With the Cell and Gene Therapy (CGT) field expanding at an unprecedented pace, driven by a surge in clinically-relevant discoveries, two core cell culture applications continue to define the landscape. Explore the stories behind the large-scale cell manufacturing below.
Whilst manufacturing workflows for cellular and recombinant products present similar, nature of the respective therapies can differ substantially. © Green Elephant Biotech.
There is no doubt that Cell and Gene Therapy (CGT) field represents a transformative chapter in the history of modern medicine. Not long ago, the pharmaceutical industry mainly concentrated on small-molecule drugs, defined by the golden age of antibiotics in the early 1940s to late 1960s. The rise of biologics and later CGTs marked a remarkable shift from chemically synthesized compounds to living systems capable of designing and producing therapies themselves. At its core, CGT is an umbrella term encompassing technologies that use living cells, genes, or both to restore or enhance biological function.
In some cases, cells are the therapy products, collected to be genetically re-engineered and returned to the patient (e.g., allogenic vs. autologous therapies). This concept is not entirely new, as early forms of cell-based treatments, such as blood transfusions and bone marrow transplants, have existed for longer than any reader of this article. What has changed, however, is the extent of precision and personalization, which allow a targeted approach for the treatment of inherited conditions, oncology and more (1).
In other instances, cells act as the producers that synthesize the drug rather than being the therapy themselves. Thanks to advances in recombinant DNA technology, researcher can programm mammalian cells, such as CHO and HEK-293, to synthesize complex therapeutic molecules like antibodies (Ab), proteins or enzymatic factors that cannot be manufactured otherwise. If therapy would be portrayed as a tool, then these cells represent both the architects and the engineers, making the design decisions that define the final product (2).
What unites these approaches is the ongoing challenges associated with the scale of supply. Whether cells are the medicine or the machinery, the number of adherent cells required to meet patient demand far exceeds the number of available donors. As over 60% of cells used in regenerative medicine represent adherent cell (3), one of the central bottlenecks associated with the current CGT landscape is a cost-effective and scalable production. This article summarizes examples for the use of mammalian cells as therapies and therapy producers and how they are slowly forming the cornerstone of healthcare.
The safest treatment are one’s own cells
Aside from stem cell transplantation, one of the most recognized examples of cell-based gene therapy is Chimeric Antigen Receptor (CAR) T-cell therapy — a form of personalized immunotherapy. Abecma (a.k.a., idecabtagene vicleucel) is one such allogeneic therapy approved by the FDA in 2021 for the treatment of multiple myeloma, a cancer of the bone marrow. Like other CAR T-cell treatments, Abecma begins with the collection of the patient’s own white blood cells, which are then genetically modified, typically using a viral vector, to express synthetic CARs (4).
This modification is crucial, as the engineered CAR structure enables T-cells to recognize and bind specific antigens found predominantly on cancer cells, enhancing the precision of the immune response. Differences in CAR design, including the signaling domains and co-stimulatory elements, influence how T-cells activate, proliferate, release cytokines, and kill malignant cells. Once the modified cells are successfully expanded, the resulting CAR T-cell population is re-infused into the patient (5).
Despite its transformative potential, CAR T-cells are rarely a first-line treatment. For instance, Abecma is indicated only after a patient has received at least two prior treatments, and its administration is supported by additional drugs designed to mitigate the adverse effects (4). Such precautions are essential, as immunological risks, including but not limited to Cytokine Release Syndrome (CRS) can arise when activated CAR T-cells indiscriminately target antigens also present on healthy tissues, causing collateral damage to nearby cells or even organ systems.
Furthermore, therapeutic potency can be hindered by the tumor microenvironment, where cancer cells create an immunosuppressive state that limits T-cell signaling and expansion (6). Yet, scientific innovation continues to refine CAR T-cell design and safety, also utilizing adherent induced pluripotent stem cells (iPSCs) for allogenic therapy generation to treat numerous blood cancers (3). Next-generation modification tools, such as CRISPR-Cas9, and preventive protocols are actively being implemented to overcome these limitations and maximize therapeutic success.
Viruses known for their ability to cure
The earliest biological therapeutics derived from cells were natural proteins such as insulin and uncharacterized polyclonal Ab, marking the start of biopharmaceutical innovation (2). Most cells cannot produce recombinant proteins or life-saving biologics on their own and must first be genetically modified — often through the use of a viral vector. The importance of safety in this approach was underscored by the Jesse Gelsinger case in 1999, where a severe immune reaction to a viral vector led to his death. In the decades since, extensive research has yielded a far deeper understanding of how to safely and effectively employ viruses in medicine. Today, adeno-associated viruses (AAVs) and lentiviruses (LVs) stand among the most widely used vectors.
AAVs are particularly valued because they are not linked to any known human disease and rarely trigger strong immune responses, yet can support long-term gene expression without integrating into the host genome. These qualities have made AAV vectors key in gene therapies for disorders such as spinal muscular atrophy (e.g., Zolgensma) and Leber congenital amaurosis (e.g., Luxturna). LV vectors, by contrast, do integrate into the host genome, ensuring stable and durable expression with comparatively low immunogenicity (7). Many CAR T-cell therapies discussed earlier similarly rely on this vector system.
A particularly well-studied and impactful example of recombinant expression in a mammalian cell culture (e.g., adherent HEK293 and CHO cells) is hemophilia. In this context, liver cells are transduced with LV vectors to achieve stable expression of the human coagulation Factor VIII (FVIII) and its corresponding mRNA. The healthiest, highest-producing clones are then selected, expanded in bioreactors, and harvested (8).
The resulting FDA-approved therapeutics, such as Kogenate and Advate, replace the missing clotting factor and can prevent life-threatening bleeding episodes altogether. From a time when blood transfusion was the only available treatment, the cloning of the FVIII gene transformed both the management and perception of hemophilia A. Nevertheless, despite these advances, product shortages still pose a challenge in economically constrained regions — reminding us that innovation is not automatically accompanied by accessibility.
Following years of regulatory and optimization challenges, today’s CGT landscape is defined by rapid technological advancement. Emerging innovations are aimed at maximizing target cell output, let that be for multiple myeloma or hemophilia, while maintaining safety and reproducibility. As this progress seeks to expand the accessibility of CGTs without drastically increasing costs of their manufacturing, rethinking conventional cultivation and scale-up practices is no longer voluntary.
This belief drives the work of Green Elephant Biotech, where our goal is to establish effective, safe, and sustainable technologies for adherent cell growth. Our cultivation systems — CellScrew® mini, 6K, and 10K, provide extensive surface availability and have been validated across a variety of mammalian cell lines, including adherent HEK-293, iPSCs, and MSCs.
Fossil-based plastics still form part of a vicious cycle in manufacturing, where the emissions generated during CGT production contribute to the climate-related diseases afflicting the patients these therapies aim to heal. By replacing fossil-based plastics with renewable and biodegradable polylactic acid (PLA), constituting CellScrew®, high performance becomes intertwined with environmental responsibility, helping to close the loop between innovation and health.
Facts before promises!
Access the experimental data and handling details for our CellScrew® and Green Elephant ® 96-well microPLAtes product lines here. Join us as part of the future today.
References:
- Kirouac, DC & Zandstra, PW, The Systematic Production of Cells for Cell Therapies (2008), Cell Stem Cell, pp. 369-381. doi: 10.1016/j.stem.2008.09.001.
- Fischbach, MA, Bluestone, JA, Lim, WA, Cell-Based Therapeutics: The Next Pillar of Medicine (2013), Sci Tranl Med, pp. 179-186. doi: 10.1126/scitranslmed.3005568.
- Efficiently manufacturing high-quality cell and gene therapies (2023). Green Elephant Biotech. Available https://greenelephantbiotech.com/blog/efficiently-manufacturing-high-quality-cell-and-gene-therapies/ (Accessed 20 November 2025).
- CAR T Cells: Engineering Patients’ Immunce Cells to Treat Their Cancers (2025). National Cancer Institute. Available https://www.cancer.gov/about-cancer/treatment/research/car-t-cells (Accessed 06 November 2025).
- All About Abecma (2025). healthline. Available https://www.healthline.com/health/drugs/abecma#_noHeaderPrefixedContent (Accessed 05 September 2025).
- Wang, Z, Li, P, Zeng, X, Guo, J, Zhang, C, Fan, Z, Wang, Z, Zhu, P, Chen, Z, CAR-T therapy dilemma and innovative design strategies for next generation (2025), Cell Death Dis, pp. 1-16. doi: 10.1038/s41419-025-07454-x.
- Bulcha, JT, Wang, Y, Ma, H, Tai, PWL, Gao, G, Viral vector platforms within the gene therapy landscape (2021), Sig Transduct Target Ther, pp. 1-24. doi: 10.1038/s41392-021-00487-6.
- Spencer, HT, Denning, G, Gautney, RE, Dropulic, B, Roy, AJ, Baranyi, L, Gangadharan, B, Parker, ET, Lollar, P, Doering, CB, Lentiviral Vector Platform for Production of Bioengineered Recombinant Coagulation Factor VIII (2011), Mol Ther, pp. 302-309. doi: 10.1038/mt.2010.239.
