As the newest and most anticipated immunotherapy for solid cancers, CAR-NK (chimeric antigen receptor-natural killer) therapies have received increasing attention in recent years, with irreplaceable safety and efficacy advantages over CAR-T. Alfa Cytology offers a service designed to facilitate the development of highly customized CAR-NK cell therapies that are specifically targeted at pancreatic cancer.
Introduction to CAR-NK Cell Therapy
NK cells, as unique innate immune cells that exhibit rapid and potent cytotoxicity without prior sensitization or antigen recognition, can be used for cancer immunotherapy and pathogen clearance.CAR-NK cells are genetically engineered to express CAR by linking antibodies (or receptors) that recognize antigens on the surface of target cells (e.g., viral-infected cells, cancer cells) with signaling molecules required to activate the immune cells. This modification can counteract inhibitory receptors and thus enhance the specific killing effect of NK cells on target cells.
Fig. 1 Cxcr2-bound CAR-NK cells enhance anti-pancreatic cancer tumor efficacy. (Yoon J H, et al, 2024)
CAR-NK Cell Therapy for Pancreatic Cancer
Since CAR-NK therapy has only just been proposed, there are very few CAR end designs available and the experimental sample sizes are too small and lack integration. Studies have shown that inhibitory TME is a major obstacle to the effective application of CAR-NK in pancreatic cancer, but the functional status of NK cells within the TME and the mechanism of injury remain unclear. Successful CAR-NK therapy requires addressing various challenges, including designing optimal CAR structures and genetically modifying the intrinsic inhibitory and activation pathways of NK cells.
Our Services
Alfa Cytology offers a comprehensive one-stop service for the development of CAR-NK cell therapies for pancreatic cancer. The service covers every stage of development, from initial design and engineering of CAR constructs to in vitro and in vivo testing of CAR-NK cells.
CAR Structure Design and Engineering Services
We help our clients design and customize CAR constructs. This includes the generation of single-chain variable fragments (scFvs) that recognize the target antigen, the design of co-stimulatory and signaling domains, and the optimization of CAR expression in NK cells, to enhance NK cell activation, proliferation, and cytotoxicity against pancreatic cancer cells, where we focus:
Chemokine Receptor Integration
Modify CAR-NK cells to express chemokine receptors that enhance their homing ability to pancreatic tumors by responding to the chemokine gradients in the tumor microenvironment.
Immunosuppressive Resistance Design
Engineer CAR-NK cells with resistance to immunosuppressive factors within the pancreatic tumor microenvironment, such as TGF-β, to sustain their activity and persistence.
NK Cell Isolation and Engineering Services
NK Cell Isolation
Isolation of high-purity NK cell populations from peripheral blood using advanced sorting techniques.
Gene Editing and Modification
Enhance NK cell function by knocking out inhibitory receptors or upregulating activating receptors.
CAR-NK Cell Expansion
Robust expansion of CAR-NK cells to generate sufficient cell numbers and maintain potency for therapy.
Enhanced Survival Engineering
Engineer NK cells with cytokine support (e.g., IL-15 transgene) to enhance their survival in vivo.
Preclinical Research Modeling Services
In vitro models
In vivo models:
The scope of Alfa Cytology's services includes identification of suitable antigens, generation of CAR constructs, engineering of NK cells, and rigorous evaluation of therapeutic efficacy and safety in preclinical models. Please contact us to discuss how these advanced CAR-NK cell therapies can be integrated into your R&D pipeline.
Reference
- Yoon J H, et al. Empowering pancreatic tumor homing with augmented anti-tumor potency of CXCR2-tethered CAR-NK cells. Molecular Therapy Oncology. 2024, 32(1).
