CAR technology in cancer therapy: from CAR-T to CAR-NK

cImmunotherapy based on it is a targeted approach to cancer treatment that continues to evolve beyond its early successes in treating leukemia. Researchers are using new technologies, such as chimeric antigen receptors (CARs) expressed on the surface of immune cells, to effectively target hematological diseases and solid tumors with cell therapy.^1,2

Development of safe and effective CARs

To develop CARs, scientists design hybrid molecules made of T-cell receptors and antibody fragments. These receptors direct immune cells to recognize and destroy cancer cells that express a specific antigen targeted by the CAR antibody domain. In recent years, scientists have refined CAR therapies to improve safety and efficacy. Optimized CAR molecules have high target antigen specificity, enable efficient activation of immune cells, and cause minimal off-target effects.^3,4

Once an optimal CAR is developed, researchers use reliable lentiviral packaging methods to transfer it to immune cells for CAR expression and quality control experiments such as immunoassays and cell viability assays. CAR-T therapies, T cells equipped with CAR expression, continue to lead the way in cell-based therapeutics. Therefore, researchers must design CAR molecules in such a way as to ensure the durability and persistence of CAR-expressing immune cells in the body.^2–6

Put CAR into cell therapy

For CAR-T cell therapy, researchers genetically engineer T cells derived from a patient or donor, modify them to express CAR, expand the cells ex vivo, and infuse them into the bloodstream of a patient As of 2017, more than 700 CAR-T therapy clinical trials have been registered, and the FDA has approved six CAR-T therapies for the treatment of hematologic malignancies, including leukemia, lymphoma, and multiple myeloma.¹ However, despite their clinical importance, there are limitations to producing and employing CAR-T therapies. Collecting T cells from a patient or donor is expensive and time-consuming, especially for patients with compromised immune systems. In addition, CAR-T cell therapy can cause serious side effects such as cytokine release syndrome (CRS) or neurotoxicity. Finally, CAR-T cells struggle to penetrate the tumor microenvironment (TME), which can hinder their therapeutic function.^3,4

To overcome conventional CAR-T limitations, researchers are turning to promising new CAR strategies. In multi-target CAR-T, scientists design CARs that recognize two or more antigens per receptor, resulting in broader immune coverage. Another novel pathway involves alternative immune cell types, such as natural killer (NK) cell therapies. Part of the innate immune response, NK cells can eliminate abnormal cells, including tumor cells and virus-infected cells. Researchers produce CAR-NK cell therapies using the same receptor-antigen hybrid technology as CAR-T, but express the CAR on the NK cells. Scientists can derive NK cells from a variety of sources, including umbilical cord blood (UCB), peripheral blood (PB), human induced pluripotent stem cells, human embryonic stem cells, hematopoietic stem cells, and NK cell lines. Compared to CAR-T therapy, CAR-NK cell therapy is safer with a lower likelihood of negative immune side effects, more efficient antitumor activity, and greater efficiency for commercial production. CAR-NK cell therapies for solid tumors and hematologic malignancies have shown promising results in clinical trials.^1,3,6,7

Complex development, comprehensive solutions

Before cell therapies reach the clinic, scientists develop them through a multistep process. Whether the therapy is CAR-T or CAR-NK, researchers must harvest immune cells, use genetic engineering to create a targeted CAR, transduce immune cells for CAR expression, culture and expand the CAR-expressing cells and test for quality control.

As the world’s leading provider of bioreagents and CRO services for the biopharmaceutical field, Sino Biological offers comprehensive solutions for scientists developing CAR-T and CAR-NK cell therapies.^5,6 These solutions cover every step from CAR development to CAR-T and CAR-NK cell preparation and cell quality control. Sino Biological’s reagents and services can support researchers during every stage of cell therapy development, from early target discovery to the preclinical phase.

References

1. AR Saez-Ibañez et al., “Cancer cell therapy landscape: trends and real-world data,” Nat Rev Drug Discov21(9):631-32, 2022. doi: 10.1038/d41573-022-00095-1
2. K. Skorka et al., “The application of CAR-T cells in hematological malignancies,” Arch Immunol Ther Exp (Warsz)68(6):34, 2020. doi: 10.1007/s00005-020-00599-x
3. “New Cancer Therapies Using CAR Technology: CAR Applications in Non-T Cells”, Sino Biologicalhttps://www.sinobiological.com/resource/application-note/novel-cancer-therapies-using-car-technology, accessed April 25, 2023
4. “CAR-T: a promising cell therapy for cancer treatment”, Sino Biologicalhttps://www.sinobiological.com/resource/application-note/car-ta-promising-cell-therapy-for-cancer-treatment, accessed April 25, 2023
5. “Comprehensive CAR-T Therapy Development Solutions,” Sino Biologicalhttps://www.sinobiological.com/category/car-t-cell-immunotherapy, accessed April 25, 2023
6. “Unique Research Support for CAR-NK Therapy,” Sino Biologicalhttps://www.sinobiological.com/category/solutions/car-nk-therapy, accessed April 25, 2023
7. KE Ruppel et al., “Learning from CAR-T cells and going beyond: tailoring the design and signaling of CAR-NK cells in cancer therapy,” Front Immunol13:822298, 2022. doi: 10.3389/fimmu.2022.822298