Title:

Engineering allorejection-resistant NK cell therapies

Speaker:

Dr. Karen Martin

Affiliation:

Oslo University

When:

Wednesday, February 5, 2025 at 11:00:00 AM   Add to Calendar

Where:

GTMI Building, Room 114

Host:

Dr. Ankur Singh
ankur.singh@me.gatech.edu

Abstract

Allogeneic cellular immunotherapies, where immune cells from healthy donors are infused into patients, have the potential to revolutionize cancer treatment due to their cost-effectiveness, scalability, and on-demand availability. However, the immunogenicity and limited persistence of allogeneic cells remain significant obstacles to achieving sustained and robust antitumor responses with these therapies. A common strategy to address the immunogenicity of allogeneic cells is genetic knockout of HLA molecules, surface proteins involved in presenting antigens to T cells, which efficiently abrogates T cell-mediated rejection. However, the loss of these HLA molecules triggers rejection by host natural killer (NK) cells via missing-self recognition. Thus, it is necessary to combine NK cell-targeted immunomodulatory strategies with HLA knockout in order to fully protect allogeneic cells from the host immune system. In this seminar, I will first demonstrate that knocking out key adhesion ligands within the immune synapse, specifically ICAM-1 and CD58, broadly protects allogeneic iPSC-derived NK cells from host NK cell-mediated rejection. I will then discuss how I am extending this approach to the ADAPT NK cell platform, a highly cytotoxic, ex vivo-expanded primary NK cell platform poised to enter clinical trials. In this context, I am developing a one-shot approach to adhesion ligand knockdown by incorporating microRNA-based shRNAs into the chimeric antigen receptor (CAR) plasmid, enabling simultaneous enhancement of ADAPT NK cell functionality and resistance to allorejection. I will conclude the seminar by outlining my vision for my future lab, where I aim to integrate my expertise in NK cell engineering with my background in biomaterials to develop next-generation NK cell therapies for the treatment of solid tumors and immune-mediated diseases.

Biography

Dr. Karen Martin is a postdoctoral researcher in the laboratory of Dr. Karl-Johan Malmberg at Oslo University Hospital. Her current work focuses on the development of off-the-shelf, allogeneic NK cell therapies for cancer. She earned her Ph.D. in Bioengineering from the Georgia Institute of Technology, working in the lab of Dr. Andrés García to create novel synthetic biomaterials for mesenchymal stem cell delivery in regenerative medicine applications. Prior to graduate school, she earned her B.S. in Mechanical Engineering from Cornell University. Her future research program will focus on advancing off-the-shelf NK cell-based immunotherapies for cancer and immune-mediated diseases through innovative biomaterials and synthetic biology approaches.

Notes

Refreshments will be served.