Project Immunoengineering for cancer immunotherapy: Reprogramming natural killer cells in cancer Program Pharmacy Term Academic Year 2023 Status Accepted Research Area Cancer research, immunotherapy, cancer biology, cell-based therapy Description Many cancers, such as glioblastoma - the most aggressive brain tumor - have no cure and don't respond to traditional drugs. Immunotherapy with genetically-engineered natural killer (NK) cells is a transformative new therapeutic modality with tremendous promise for uncurable cancers. The goal of this OUR Scholar research program is to develop cutting-edge cell-based immunotherapies for cancer with engineered natural killer (NK) cells by targeting mechanisms of immunosuppression in the tumor microenvironment. Specifically, the project is focused on engineering the immune functions of NK cells to generate genetically-engineered CAR-NK variants of NK cells to specifically interact with the tumor microenvironment and rescue NK cell activity from dysfunction and result in durable anti-tumor responses. In this context, the project will characterize and optimize a new multi-specific engineered NK cells for the treatment of glioblastoma, designed to co-target multiple elements of NK cell dysfunction in the brain tumor microenvironment. This project builds on the lab’s recent publication describing the very first triple-engineered NK cell platform for GBM addressing antigen escape and immunometabolic reprogramming , and will incorporate elements that reprogram the cells’ metabolic function. These engineered NK cells will be developed from induced pluripotent stem cells as well as peripheral blood. Supervisor Sandro Matosevic Mentor Type of work required This is a hands on project in a lab which will enable the student to gain and develop skills in cancer research, human immunology, cell culture, immune cell treatment, synthetic biology and bioengineering. The student’s role in the project will be to isolate and differentiate immune cells, characterize and learn how to effectively engineer these cells to express various multispecific constructs, learn how to manipulate NK cell activity in the context of metabolic modulation , and perform functional assays including cytotoxicity, degranulation and immunophenotyping.
The student will also be involved in learning some computational analysis to analyze RNAseq and CRISPR screen data. The student will learn skills incell-based immunotherapy and immunoengineering, cancer biology, cell therapy product development and formulation, synthetic biology and genetic engineering.

In terms of lab participation, the student will be involved in weekly lab meetings with the rest of the lab where they will present their findings, and in regular individual meetings with the PI. The student will be trained and mentored by a graduate student. Websites http://www.matoseviclab.com Qualifications No prior experience required. Credit Hours 0 Weekly Hours 30 (estimated)