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A Modular TanCAR T-Cell Framework Targeting Schistosomiasis-Associated Bladder Cancer: An In Vitro Study

Bladder Cancer is the 7th most common cancer among males and 17th among females. Egypt ranks 10th amongst the countries with highest bladder cancer incidence rates. This has been attributed to endemic parasitic infestation with Schistosoma Hematobium. Schistosomiasis-associated bladder cancer constitutes 60% of cases. 

In our project, we aimed to engineer the chimeric antigen receptor T-cells capable of targeting schistosomiasis-associated bladder cancer cells as well as overcoming the immuno-suppressive conditions associated with the tumor microenvironment. To achieve this purpose, we devised a computational framework for antibody design producing single chain variable fragments which target intracellular antigens. 

We then engineered dual 4th generation TanCAR-T cells (using CRISPR-CAS9) with enhanced cytokine production and a dual functionality against cancer cells as well as the egg form of the parasite. We also optimized the CAR design by directed silencing of exhaustiveness-inducing transcription factors utilizing a computational pipeline for designing and optimizing silencing RNAs cassettes.

Project Description




Human Practices