Chimeric Antigen Receptor T-cell (CAR-T) therapy represents a groundbreaking approach in the fight against pancreatic cancer (PC). Alfa Cytology's CAR-T cell therapy development service involves optimizing CAR design, improving T-cell persistence and function, and identifying novel tumor-associated antigens. We are dedicated to enhance the efficacy and safety of CAR-T cell therapy for pancreatic cancer.
Overview of CAR-T Cell Therapy for Pancreatic Cancer
CAR-T cell therapy, which uses genetically engineered T-cells redirected to specific cancer-associated antigens to trigger potent cytotoxic activity, has emerged as a promising therapeutic strategy for a wide range of hematologic malignancies, and to date has been widely used as an individualized treatment. However, the food and drug regulatory agencies has not yet approved its use for the treatment of solid tumors. Nonetheless, CAR-T cell therapy remains a promising immunotherapeutic strategy for pancreatic cancer, a solid cancer that is resistant to standard tumor therapies.
Fig. 1 Isolation, engineering, and challenges of CAR T cell therapy in pancreatic adenocarcinoma (PDAC). (Akce M, et al, 2018)
Pre-clinical Studies on CAR-T Cell Therapy in Pancreatic Cancer
Researchers have conducted numerous studies on the application of CAR-T cells for PC therapy in animal or human cell line models with the aim of identifying suitable tumor-associated antigens (TAA), as well as evaluating the toxicity and efficacy of CAR-T cells, with exciting results.
| Model | Targeted Tumor Antigen | Type of CAR-T Cells |
|---|---|---|
| In vitro and in vivo | CEA and MSLN | Dual receptor (anti-CEA and anti-MSLN) CAR-T cells |
| In vitro and in vivo | MSLN | Anti-MSLN CAR-T cells |
| In vivo | CEA | IL-18-secreting CAR-T cells |
| In vitro and in vivo | CD70 | Anti-CD70 CAR-T cells expressing CXCR1 and CXCR2 |
| In vitro and in vivo | Trop2 | Anti-Trop2 CAR-T cells |
| In vitro and in vivo | PD-1 | PD1-Dap10-CD3zeta CAR-T cells |
| In vitro and in vivo | NKG2D | NKG2D CAR-T cells with deleted 4.1R protein |
| In vitro and in vivo | MSLN | CAR-T cells with ICOS |
| In vitro and in vivo | ROR1 | SCFAs—modified CAR-T cells |
Our Services
Alfa Cytology's one-stop CAR-T cell therapy development service provides a comprehensive, integrated approach to preclinical research. The service covers all aspects of CAR-T cell therapy development, ensuring a streamlined and efficient process that overcomes the unique challenges posed by the pancreatic cancer tumor microenvironment.
Workflow of CAR-T Cell Therapy Development for Pancreatic Cancer
Target Antigen Discovery
Identification of specific TAAs expressed on pancreatic cancer cells through advanced genomic and proteomic approaches.
CAR Design and Engineering
Construction of CARs with optimized antigen-binding domains, co-stimulatory signals, and intracellular signaling motifs to enhance T-cell activation and persistence.
T-Cell Transduction and Expansion
Genetic modification of patient-derived T-cells using viral or non-viral vectors to express CARs, followed by ex vivo expansion to achieve a therapeutically relevant cell dose.
In Vitro Efficacy Testing
Assessment of CAR-T cell cytotoxicity, proliferation, and cytokine production against pancreatic cancer cell lines in controlled laboratory settings.
In Vivo Preclinical Studies
Evaluation of the anti-tumor efficacy and safety of CAR-T cells in animal models of pancreatic cancer, including assessments of tumor regression, survival benefit, and off-target effects.
Safety and Toxicity Assessment
Comprehensive evaluation of potential toxicities, including cytokine release syndrome (CRS) and off-target cytotoxicity, to ensure the safety profile of the CAR-T cells.
Alfa Cytology's CAR-T cell therapy development services for pancreatic cancer offer a comprehensive and integrated approach to preclinical research. We employ cutting-edge technologies and innovative strategies to overcome the unique challenges of pancreatic cancer and ensure the development of highly effective and safe CAR-T cell therapies. For more information or to establish a partnership, please contact us directly.
References
- Akce M, et al. The Potential of CAR T Cell Therapy in Pancreatic Cancer. Front. Immunol. 2018, 9:2166.
- Czaplicka A, et al. Chimeric Antigen Receptor T Cell Therapy for Pancreatic Cancer: A Review of Current Evidence. Cells. 2024, 13(1):101.
