Alfa Oncology is proud to offer CAR-T therapy development services for PC. Our services include the production of autologous and allogeneic CAR-T cells. In addition, we also offer PDAC models to evaluate cellular immunotherapy.
A promising therapeutic modality for PC
CAR-T cell therapy generally involves collecting T cells from individuals, genetically engineering them to express a type of CAR-T cell that can recognize and attack cancer cells, and then systematically injecting these cells into the body to exert anti-tumor activity. Among CAR-T cells, CAR is a fusion protein composed consisting of an extracellular antigen-binding domain attached to endodomain(s) that is responsible for downstream signaling. To date, five generations of CARs have been developed. The latest generation of CAR has the capability to enhance the proliferation and antitumor activity of CAR-T cells through the insertion of interleukin (IL)-2Rβ, which induces antigen-dependent activation of the JAK-STAT pathway.
Fig. 1 Some candidate target antigens for CAR-T cell therapy in PDAC.
- Candidate target antigens for CAR-T cell therapy in pancreatic ductal adenocarcinoma (PDAC)
MSLN is usually expressed at limited levels on the cell surface through the mesothelial tissue of the body; however, it is overexpressed in many solid tumors, including PDAC, lung adenocarcinoma, ovarian adenocarcinoma, and mesothelioma. It is currently one of the most tested immunotherapeutic target antigens in PDAC.
CD133 is a transmembrane glycoprotein expressed by hematopoietic cells and epithelial cells. It is found to be highly expressed in PDAC cancer stem cells.
-Epidermal growth factor receptor (EGFR)
EGFR is a transmembrane protein that binds to the extracellular EGF family of proteins and has been detected in up to 90% of PDAC patients.
-Human epidermal growth receptor 2 (HER2)
HER2 is a cell surface transmembrane glycoprotein in the EGFR family of proteins. HER2, an essential mediator of cellular activity, has been found to be overexpressed in 60% of PDAC patients.
CAR-T cell therapy is an active, viable, and promising area of research that is still being explored in PC. Based on CAR design and selection of more than one targetable antigen, CAR-T cell therapy can improve its efficacy and overcome tumor heterogeneity. Moreover, the on-target/off-tumor toxicity of this therapy can be minimized by selecting tumor-restricted antigens. Our team of experts has years of extensive experience in developing CAR-T therapy for PC. We are able to provide a one-stop solution for CAR-T cells, including antigen identification, CAR-T cell design, isolation, engineering, and expansion.
- Production of autologous CAR-T cells
T cells are first collected from the peripheral blood of PDAC patients by leukapheresis. Then, they are engineered to express chimeric antigen receptors that target specific tumor antigens. Finally, these cells are subsequently expanded and then reinfused into the patient.
- Production of allogeneic CAR-T cells
Allogeneic CAR T cells from healthy donors have advantages over autologous CAR T cells, including their immediate availability, product standardization, and reduced cost. This is primarily because T cells from healthy donors can be expanded exponentially and cryopreserved so that off-the-shelf products can be produced without production or treatment delays.
- A range of PDAC models to evaluate cellular immunotherapy
The efficacy and safety of CAR-T treatments will be tested in preclinical models prior to translation to human clinical trials. We offer a range of PDAC models for preclinical CAR-T studies, including PC cell model, syngeneic xenograft as well as transgenic and humanized mice.
For more about our services, please contact us. We are glad to work with you!
- Yeo, Dannel, et al. "The next wave of cellular immunotherapies in pancreatic cancer." Molecular Therapy-Oncolytics (2022).
- Akce, Mehmet, et al. "The potential of CAR T cell therapy in pancreatic cancer." Frontiers in immunology 9 (2018): 2166.