Engineering and Reprogramming Natural Killer Cells for Immunotherapy of Cancer

Immune cell therapies hold tremendous potential in the treatment of cancer. Among immune cells, natural killer (NK) cells have a powerful innate ability to recognize and eliminate tumor cells. However, in the microenvironment of tumors, especially solid cancers, NK cell numbers are low, and those cells that are able to infiltrate these tumors are dysfunctional. In order to develop NK cell immunotherapies able to overcome aggressive mechanisms of suppression in tumors and enable them to more specifically target various cancers, genetic engineering approaches have been utilized to immunometabolically reprogram and enhance the function and specificity of NK cells against cancer. These genetically-engineered cell-based therapies have been formulated into clinical products and used to treat diverse cancers. This talk will give an overview of emerging engineered cell-based therapies, and how targeting mechanisms of immunometabolic suppression can yield functionally competent immune cells. Finally, the seminar will discuss how gene and cell engineering can be leveraged to generate powerful engineered NK cells, including multispecific and tumor-responsive variants, as well as new developments in the generation of allogeneic, off-the-shelf immunotherapies based on iPSC-derived NK cells, able to tackle complex mechanisms of treatment resistance in cancer. 

Learning Objectives:

1. Define the principles of cell-based therapies.

2. Outline approaches and targets for genetic engineering of immune cell therapies.

3. Describe applications and challenges of cell-based therapies in therapeutic settings.