Z. Zhang (Zhaobao)
Promovendus - Systems Chemistry
Dendritic cells are antigen-exposing cells that activate T-cells for elimination of cells containing pathogens such as bacteria or viruses, but can also be used to activate T-cells for elimination of cancer cells. Recent efforts in cancer immunotherapy has been directed to the development of artificial DCs that mimic natural DCs, in particular biomimetic polymers or nanoparticles loaded with antibodies, with the goal to trigger an efficient and specific response for elimination of tumor cells.
To develop a new class of artificial dendritic cells for immunotherapy that is more versatile, easier to produce and more cost-efficient than existing ones and can be tailor-made for individual patients. We make use of recently discovered biomimetic polymers in our institute, which are based on helical polyisocyanide peptides. These polymers are functionalized with DNA aptamers (sgc8c) that specifically bind to leukemia cell surfaces, like DCs. The above-mentioned sgc8c is identified using an unbiased whole-cell SELEX approach that targets protein tyrosine kinase 7 (PTK7). Subsequently, our polymer-based DCs is used for co-culture with leukemia cells. As a result of stiffness changes on the surrounding cell matrix caused by DCs, we observe a clear reduction in cell proliferation of leukemia cells. Further study into the molecular mechanism will give more evidence of our novel DCs, which is biocompatible and non-toxic. These findings demonstrate the potential of our functionalized polymers for mimicking natural DCs, paving the way for their exploitation in immunotherapeutic strategies. If successful, the approach can be applied for personalized anticancer treatment by obtaining patient T-cell samples and screening for aptamer-based DCs to boost the patient's immune response.
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- ZHANG, X. P., HOU, L., ZHANG, L. F., NIE, K., ZHANG, Z. B., & TIAN, J. Z. (2013). Effect of Xingnao Yizhi Capsule with Different Proportions on Learning and Memory Abilities in Alzheimer's Disease Rats. Chinese Journal of Experimental Traditional Medical Formulae, 19, 060. Volledige tekst