Cellular and gene therapy is a rapidly growing area of research, evidenced by the growing number of products advancing into clinical development.
By the end of 2023, the United States FDA has listed a cumulative total of 34 approved cellular and gene therapy products that have completed development.
These emerging classes of biologics offer the potential to effectively treat or mitigate previously untreatable conditions, ranging from various cancers, genetic conditions, blood disorders, and other difficult-to-treat conditions.
What are the current methods of cell and gene therapy?
In cell therapy, patients are given cells that have undergone genetic modification or preparative treatment to produce a therapeutic effect.
These include cells obtained from the same patient (autologous) or other donors (allogeneic).
Cellular therapy products that have received approval include CAR-T cell immunotherapies, stem and progenitor cells, activated immune cells, and processed tissue or cell types.
Gene therapies manipulate or modify gene expression to alter the properties of living cells and produce a specific therapeutic effect.
This is done by introducing transgenes via vectors such as recombinant viruses or non-viral carrier complexes.
Approved gene therapy products include human transgenes carried by adenoviral, AAV, or HSV vectors to treat diseases like hemophilia, Duchenne muscular dystrophy, and certain cancers.
The tables below further highlight several cell and gene therapies that have received approval from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).1,2
What tools are used in developing cell and gene therapies?
Cell-based therapies rely on the proper isolation, expansion, and viability of human cells and will require appropriate tools and reagents.
Cell sorters
and
flow cytometers
are central to obtaining the desired cell populations and characterizing their identity and functions.
To ensure optimal cell health, high-quality media reagents should be used, such as those specially formulated for culturing human tissue or stem cells.
In gene therapy development,
CRISPR-based
tools enable genomic editing of target genes.
Vector constructs
and transfection reagents are also required for proper transgene delivery.
Browse a wide variety of product categories to discover solutions for use in cell and gene therapy research and development.
What are some guidelines for cell and gene therapy development?
As vectors are important components in gene modification, their safety and quality should be sufficiently characterized throughout development.
Vectors that integrate into cellular DNA can provide long-term transgene expression in comparison to non-integrating vectors.
Longer-term follow-up studies would be prudent when using integrating vectors to account for potential risks of delayed adverse events.
Other considerations for vector integration include the risk of altering the expression of cellular genes, contributing to tumorigenicity.
Testing for modified cells, such as CAR T, generally requires complex assays and the development of product-specific biological assays.
Proper assay development in the early stages of development can help ensure a successful final product.
Ideal assays should use scientifically sound principles, be specific, sensitive, reliable, and include appropriate controls or standards.
Techniques such as flow cytometry can be used to assess cell viability, identity, purity, and strength throughout the manufacturing process.
Assays should be conducted to measure transgene presence and expression, as well as the intended cellular composition of the final product.
Needless to say, the target antigen should be well understood.
Knowledge of the antigen’s tissue expression profile as well as any clinical insights can help address risks for potential off-targets.
Uncontrolled cell proliferation can also be assessed in vitro and in vivo using methods such as T cell clonality testing, karyotypic analysis, TCR repertoire analysis, and ex vivo stimulation and recognition assays.
Approved Cell Therapies
| Trade Name | Company | Disease | Description |
|---|
| ABECMA 1,2 | Celgene | autologous immunotherapy using BCMA-directed CAR T-cells | multiple myeloma |
| ALLOCORD 1 | SSM Cardinal Glennon Children's MC | allogeneic restoration of blood counts and function using HSCs | hematopoietic system disorders |
| ALOFISEL 2 | Takeda Pharma A/S | allogeneic immunomodulation by donor-derived expanded adipose stem cells | Crohn’s disease |
| BREYANZI 1,2 | Juno Therapeutics | autologous immunotherapy using CD19-directed CAR T-cells | large B-cell lymphoma (LBCL) |
| CARVYKTI 1,2 | Janssen Biotech | autologous immunotherapy using CD19-directed CAR T-cells | multiple myeloma |
| CASGEVY 1 | Vertex Pharmaceuticals | reduce BCL11A expression in erythroid lineage cells using autologous CRISPR-edited HSCs | sickle cell disease |
| CLEVECORD 1 | Cleveland Cord Blood Center | allogeneic restoration of blood counts and function using HSCs | hematopoietic system disorders |
| DUCORD 1 | Duke University | allogeneic restoration of blood counts and function using HSCs | hematopoietic system disorders |
| EBVALLO 2 | Pierre Fabre Medicament | allogeneic EBV-specific T-cell immunotherapy | Epstein-Barr virus positive post-transplant lymphoproliferative disease (EBV+ PTLD) |
| GINTUIT 1 | Organogenesis | allogeneic application of a scaffold containing human keratinocyte and fibroblast cells | mucogingival conditions |
| HEMACORD 1 | New York Blood Center | allogeneic restoration of blood counts and function using HSCs | hematopoietic system disorders |
| KYMRIAH 1,2 | Novartis Pharmaceuticals | autologous immunotherapy using CD19-directed CAR T-cells | follicular lymphoma |
| LANTIDRA 1 | CellTrans | allogeneic transplantation of donor pancreatic islet cells for insulin production | Type 1 diabetes |
| LAVIV 1 | Fibrocell Technologies | injection of autologous expanded dermal fibroblasts | nasolabial fold wrinkles |
| MACI 1 | Vericel Corporation | autologous implantation of cultured chondrocytes | cartilage defects of the knee |
| OMISIRGE 1 | Gamida Cell | allogeneic restoration of blood counts and function using HSCs | hematologic malignancies |
| PROVENGE 1 | Dendreon Corp. | autologous immunotherapy using CD54+ cells activated with PAP-GM-CSF | prostate cancer |
| RETHYMIC 1 | Enzyvant Therapeutics | allogeneic donor thymic tissue for the development of naïve immunocompetent recipient T cells | congenital athymia |
| STRATAGRAFT 1 | Stratatech Corporation | allogeneic donor-derived metabolically active keratinocytes and fibroblasts | thermal burns |
| TECARTUS 1,2 | Kite Pharma | autologous immunotherapy using CD19-directed CAR T-cells | mantle cell lymphoma, acute lymphoblastic leukemia |
| YESCARTA 1,2 | Kite Pharma | autologous immunotherapy using CD19-directed CAR T-cells | large B-cell lymphoma |
Approved Gene Therapies
| Trade Name | Company | Disease | Description |
|---|
| ADSTILADRIN 1 | Ferring Pharmaceuticals | gene delivery of the human interferon alfa-2b via an adenoviral vector | bladder cancer |
| ELEVIDYS 1 | Sarepta Therapeutics | gene delivery of a micro-dystrophin protein via an AAV vector | Duchenne muscular dystrophy |
| HEMGENIX 1 | CSL Behring | gene delivery of a human Factor IX protein variant via an AAV vector | Hemophilia B |
| IMLYGIC 1 | BioVex | gene delivery of human GM-CSF via an HSV-1 vector | melanoma |
| LUXTURNA 1 | Spark Therapeutics | gene delivery of human RPE65 via an AAV vector | retinal dystrophy |
| LYFGENIA 1 | bluebird bio | autologous cell-based gene therapy using HSCs transduced with functional ßA-globin via a lentiviral vector | sickle cell disease |
| ROCTAVIAN 1 | BioMarin Pharmaceutical | delivery of a B-domain deleted SQ form of the human coagulation factor VIII via an AAV vector | hemophilia A |
| SKYSONA 1 | bluebird bio | autologous cell-based gene therapy using HSCs transduced with functional ABCD1 via a lentiviral vector | cerebral adrenoleukodystrophy |
| VYJUVEK 1 | Krystal Biotech | gene delivery of human COL7A1 via an HSV-1 vector | dystrophic epidermolysis bullosa |
| ZOLGENSMA 1 | Novartis Gene Therapies | gene delivery of human SMN via an AAV vector | spinal muscular atrophy |
| ZYNTEGLO 1 | bluebird bio | autologous cell-based gene therapy using HSCs transduced with functional modified ßA-T87Q-globin via a lentiviral vector | ß-thalassemia |
References
1. Food and Drug Administration. Approved Cellular and Gene Therapy Products. U.S. Food and Drug Administration. Accessed Feb 2024. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products
2. European Medicines Agency. Medicines. European Medicines Agency. Accessed Feb 2024. https://www.ema.europa.eu/en/medicines
3. Research C for BE and. Considerations for the Development of Chimeric Antigen Receptor (CAR) T Cell Products. U.S. Food and Drug Administration. Published March 21, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/considerations-development-chimeric-antigen-receptor-car-t-cell-products
4. 1.Research C for BE and. Human Gene Therapy Products Incorporating Human Genome Editing. U.S. Food and Drug Administration. Published June 9, 2022. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/human-gene-therapy-products-incorporating-human-genome-editing