Breaking Tolerance to Unresponsiveness to Immunotherapy by Natural Killer Cells presents chapters by leaders in translational natural killer cell research and bridges the gap between clinical need and basic science by presenting state-of-the-art knowledge on innate immunity and the challenges associated with translating it to practical adoptive immunotherapies. New approaches, such as the genetic engineering of NK cells and their combination with checkpoint blockade therapies are discussed among other potential interventions to improve natural killer cell functionality against targets. In addition, challenges, such as the difficulty in genetically modifying NK cells or a poor understanding of their effect on checkpoint inhibition are included.
The book is a key reference and go-to resource for researchers and clinicians who want to understand the current limitations associated with bringing natural killer cell-based immunotherapies to the clinic.
- Discusses translational aspects from leaders in the field to facilitate readers' understanding of clinical challenges
- Addresses important events that occur in patient tumor microenvironments as they pertain to NK cells and how they are, or can be, tackled to overcome immunosuppression of NK cells
- Focuses on immunometabolism by discussing the metabolic reprogramming that NK cells undergo in solid tumors, including hypoxia, adenosine and other metabolites
Adelheid Cerwenka, The Medical Faculty Mannheim of the University of Heidelberg
2. Targeting purinergic signaling to improve natural killer cells immunotherapy of solid tumors
Mark Smyth, QIMR Berghofer
3. Genetic engineering of CD19-targeted chimeric antigen-receptor NK cells derived from cord blood as clinical treatment for immunotherapy of B cell lymphoma
Katy Rezvani, MD Anderson Cancer Center
4. New sources of functionally-mature NK cells: peripheral blood-derived induced pluripotent stem cells
Shu Wang, National University of Singapore
5. The contribution of natural killer cells to immunotherapy with PD-1/PD-L1 checkpoint blockade
Michele Ardolino, University of Ottawa
6. Molecular checkpoints controlling NK cell activation and anti-tumor immunity
Hun Sik Kim, University of Ulsan College of Medicine
7. Exploiting hypoxia's role in driving functional responses by IL-15-primed NK cells to target solid tumors
Holger Lindner, Heidelberg University
8. Metabolic reprogramming and the role of mTOR in driving NK cell anti-tumor immunity
Andreas Lundqvist, Karolinska Institutet
9. Allo-reactive NK cells in immunotherapy of lung cancer: a clinical perspective
Jiuwei Cui, First Hospital of Jilin University
10. Control of tumor metastasis by NK cells
Lorenzo Galluzzi, Weil Cornell Medical College
11. Challenges and opportunities with NK cells in the clinical treatment of acute myeloid leukemia
Rizwan Romee, Dana Farber Cancer Institute
As faculty in the College of Pharmacy at Purdue University, Dr. Matosevic leads an active, externally-funded research program in immunotherapy with natural killer cells. He has made important contributions to the field of NK cell immunotherapy and continues to study their reprogramming in the microenvironment of tumors and how this can be overcome to advance their use in the clinic.
Dr. Matosevic has extensive experience in cell-based therapies with NK cells. Apart from a prolific research output, he has led important initiatives in cell therapy, aimed at standardizing cell-based therapy development and manufacturing with ISO and USP, as well as having organized and co-chaired a workshop at the National Institute of Standards and Technology with an international audience of academic and industrial stakeholders. He has acted on the Communications Committee of the International Society for Cellular Therapy and continue to organize and chair academic meetings on natural killer cell-based therapies.