Genetically engineered CAR-NK cells contain a typical extracellular antigen-binding domain, a hinge and transmembrane region, and an accompanying intracellular costimulatory domain from the receptor, which represents a convergent design to effectively attack cancer cells using engineered NK cells. CAR-NK cells with favorable cytotoxicity, short lifespan, and low manufacturing costs have received much attention as a potential immunotherapeutic tool in the treatment of PC. In addition to providing CAR-T therapy development services, Alfa Oncology is also committed to providing CAR-NK therapy development services for PC.
Overview of NK cells
As one of the immune cells, NK cells are crucial effector units in tumor immunosurveillance, targeting foreign or damaged cells. NK cells have been widely used as prognostic biomarkers for a range of malignancies. In addition, they have received widespread attention as an attractive target for immunotherapy, both as cellular therapy and as a pharmaceutical target. NK cell therapy is similar to CAR-T cell therapy in that they both transform or enhance immune system cells to effectively fight cancer. Unlike T cells, NK cells can recognize targets in a non-antigen-specific manner without prior sensitization, which makes them potential candidates for cancer treatment. Thus, NK cells have been considered an alternative to allogeneic CAR T cells. Compared with T cells, NK cells as an immunotherapeutic tool have some advantages, including,
- NK cells represent a relatively safe treatment option due to their low risk of on-target/non-tumor toxicity.
- NK cells have facilitated the development of a truly "off-the-shelf" cellular immunotherapy because NK cells can potentially be derived from multiple sources.
- NK cells are naturally cytotoxic and can eliminate malignant cells in a CAR-dependent or independent manner.
Fig. 1 Sources and generation procedure of CAR-NK cells. (Marofi, Faroogh, et al., 2021)
The CAR-NK cell-mediated approach offers a promising area for innovation in cellular immunotherapy. With advanced CAR development technologies and in-depth knowledge of PC biology, we fully support CAR- NK development services for PC. Specifically, our services include, but are not limited to, the following list:
- Target identification & selection
-Selection of cell source, including peripheral blood-derived NK (PB-NK) cells, umbilical cord blood-derived NK (UC-NK) cells, and stem cell-derived NK cells
-Novel target selection for CAR-NK cells by multiple gene and protein analysis technologies
- CAR-NK cell vector design and construction
-Design and construction of different generations of CARs
-Multiple options for CAR transduction, such as lentiviral, retroviral, and other CAR-expressing vectors
- CAR-NK cell culture and expansion
-Cultivation of NK cells with specific media containing cytokines
-CAR-NK cell expansion
- CAR-NK cell in vitro assay
-CAR expression validation
-Efficacy test of CAR-NK cells
-Cytotoxicity test against target PC cells
- CAR-NK cell preclinical in vivo assay
-Multiple PC-related preclinical models available for in vivo experiments
-Efficacy test of CAR-NK cells
-Viability and bio-distribution study of CAR-NK cells
-Toxicity evaluation of CAR-NK cells
Workflow of our service
For more about our services, please contact us. We are glad to work with you!
- Zhang, Leisheng, et al. "CAR-NK cells for cancer immunotherapy: from bench to bedside." Biomarker Research 10.1 (2022): 1-19.
- Fincham, Rachel Elizabeth Ann, et al. "Natural killer cells in pancreatic cancer stroma." World Journal of Gastroenterology 27.24 (2021): 3483.
- Marofi, Faroogh, et al. "CAR-NK cell: a new paradigm in tumor immunotherapy." Frontiers in oncology 11 (2021): 2078.