Engineered Natural Killer Cells as an Effective Cancer Immunotherapy

Laboratory Study

This tandem project explores an alternative treatment strategy for cancer, based on cancer immunotherapy. The aim is to improve the safety and potentially the efficacy of CAR-equipped (Chimeric Antigen Receptors) natural killer cell products for the treatment of tumors through site-specific gene editing.

The currently available treatment options (chemotherapy and radiotherapy) have limited therapeutic outcome against cancer, and are associated with severe side effects and high risk of recurrence. Recently, immunotherapeutic agents displayed promising results in clinical cancer treatment, and have therefore attracted attention from clinicians and cancer patients worldwide. The main advantage of cancer immunotherapy compared to conventional treatments is that it treats primary cancer, and prevents metastasis and recurrence as well. Consequently, cancer immunotherapy has become a gold standard option for cancer patients. Various immunotherapeutic antibodies and cell therapeutics are constantly being developed worldwide. The use of CAR T-cells and NK-cells (natural killer cells) are also reported to destroy tumors and to possitively change of the microenvironment they are set in.

The AGYA members Mohamed Abou El-Enein (Medical and Health Sciences) and Maha Nasr (Pharmacy) are eager to identify and compare different potential CAR integration sites for NK-cells including recently described genetic safe harbor sites. Their aim is to establish a protocol for the efficient gene transfer into NK-cells using CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein) assisted targeted integration. Mohamed Abou El-Enein will assess the feasibility of engineering NK-cells for cancer immunotherapy during the first phase of the research work. As a continuation of this work he will modify these cells to optimize their ex vivo expansion and conduction of in vivo work. After the establishment and the validation of the potential of engineering NK-cells for cancer immunotherapy, the final phase of this research tandem project will be conducted by Maha Nasr focussing on the use of nanoparticles in conjugation with NK-cells in order to achieve a synergistic anticancer therapy or to use nanoparticles to deliver payload agents to NK-cells.