India's chronic kidney disease kidney disease (CKD), with a seven-fold increase in incidence during FY 2019, was declared a major chronic condition for 2018 by the World Health Organization (WHO). CKD is a group of rare but serious immune disorders that spread through the urinary system and lead to renal failure, protein excretion and chronic kidney disease progression.
This condition affects approximately one in every 1,000 people across the globe. Although there is no cure for the disease, it can lead to severe problems in daily life and limit the ability to walk or breathe. Restriction in treatment is also a major contributing factor, as the immune system is strongly involved in the disease.
The new treatment breakthrough.
It is already known that a protein called Protein Kinase A (PKA) that is crucial for the development of some known immunotherapy cancer therapies including BRAF-inhibitor therapy and Kraseniavirine (XaV) is mutated in kidney disease. Hence, the researchers decided to go for a novel approach by developing a hydrogel drug delivery system which can be used in combination with existing drugs for T-cell inflammatory disease.
Integrating PKA-targeted hydrogels into the treatment paradigm.
The hydrogel therapy platform consisted of platinum-coated metal plated polymers that were coated with a pKa-targeting drug delivery drug through a nanostructure. The treatment injected in a type of c-Myc-sphosphate-rich media was incubated with a cancer immuno-competent donor kidney cell line for a period of one week before being injected into patients receiving existing CKD treatment through dialysis.
To inhibit T-cell immunotherapy, the added drug was supplied through a combination, multi-targeting and transcription factor-neutralising (MT), cross-reactive MT-T therapy system. The system comprises a therapeutic junction (TJB) engineered from human cancer leucocyte stem cells (hCSCD) and an HT-based HT-Novartis-B-6-MOR-1 engineered HT-Novartis-R-308 plasminogen activator-R-clone HT-biotin-CB-L-130. It has been shown that total transplantation of T-cells (CT) was enhanced by using only the TJB system as the number of animals that received current chemotherapy was reduced by 50%.
We were excited to see that this therapeutic breakthrough enabled our team to gain a superior understanding of the mechanism of action of the drug delivery system, and was facilitated by the synergistic utilization of the platform technology."
Harit Chopra, principal investigator, DTC North.
- To date, it was not clear how the hydrogel drug delivery system developed during the process of conceptual proof-of-concept testing and validation could be used in renal cancer therapy. To overcome the challenge, the team developed a completely new and more potent delivery system using crystallized platinum exoskeletons.
The team carried out detailed characterization of the delivery delivery system, including neutralization of Membrane Receptor-1 (MREP) cell receptor antagonist FEBB and MREP-antenant PPARβ.
In vitro experiments with mouse models in which the drug delivery system was administered to treatment-naïve mouse kidney cancer cells indicated that the combined TJB system induced a complete T cell differentiation response in these using both cell lines and human kidney cancer cells. The generation of T-cell therapy was induced using human pluripotent cells and implanted into the mice receiving CKD-targeted vascular therapy.