Enabling clinical grade manufacturing of gene-engineered NK cells

Clinical evidence has shown that natural killer (NK) cells hold the promise for successful adoptive immunotherapy for cancer. Regulated by their germ-line encoded activating and inhibitory receptors, NK cells can recognize and eliminate tumor cells rapidly without prior sensitization. To further enhance their anti-tumor efficacy, NK cells can also be modified by chimeric antigen receptors (CARs).

One of the major obstacles to use NK cells in immunotherapy is the lack of an efficient gene transfer method for primary NK cells. Viral gene delivery to primary NK cells has always been challenging and less efficient than for other cells of the hematopoietic system.

We developed a platform for the clinical grade manufacturing of CAR NK cells using baboon envelope glycoprotein pseudotyped lentiviral vectors for highly efficient transduction. Subsequently, we transferred this concept to an automated process for CAR NK cell generation under good manufacturing practice(GMP)-compliant conditions in a closed system by using the CliniMACS Prodigy® Instrument.

Besides this, many other challenges have caused industry participants to express concerns that the manufacturing shortage would threaten industry growth and lengthen time-to-market for these new types of living therapies. Automation, upscaling and streamlining manufacturing and QC processes are key to ensure future success in the clinic.

• About the baboon envelope glycoprotein pseudotyped lentiviral vectors for highly efficient transduction of NK cells      
• Upscaling of clinical CAR NK cell manufacturing      
• Available optimized in-process and quality control for consistent CAR NK cell manufacturing

Nina Möker

R&D Reagents Manager, Allogeneic Cell Therapy, Miltenyi Biotec

Nina Möker is aR&D Reagents Manager for the development of allogeneic cell therapy for cancer at Miltenyi Biotec in Bergisch Gladbach, Germany. She is leading an innovative team with the focus of developing the comprehensive solution package for the manufacturing and analytics of engineered Natural Killer cells. For the past five years she has been working together with the Miltenyi clinical production and clinical development teams to overcome the challenges of manufacturing NK cells with high functionality in a GMP compliant and feeder cell free system. Prior to joining Miltenyi Biotec and dedicating herself to allogeneic cell therapy, Nina has gained strong experience in big and medium-sized pharma focusing on antibody- and small molecule-based drug discovery.

Evelyn Ullrich MD

Arbeitsgruppe Zelluläre Immunologie, Universitätsklinikum, Frankfurt am Main (kgu.de)

Rizwan Romee MD

Associate Professor of Medicine, Harvard Medical School, Dana Farber Cancer Institute

Dr. Rizwan Romee is an associate professor of medicine at Harvard Medical School and director of the haploidentical donor transplant program at Dana Farber Cancer Institute (DFCI), Boston. He is also the principal investigator of the Romee Lab for NK Cell Gene Manipulation and Therapy at DFCI. The research focus of his laboratory is genetic manipulation of the human Natural Killer (NK) cells to enhance their anti-tumor function and simultaneously modulate the highly immune suppressive tumor microenvironment (TME). His work at Washington University helped describe human memory-like NK cells with enhanced anti-tumor activity and he led a first in human clinical trial of these cells in patients with relapsed and refractory AML demonstrating safety and promising activity. He is currently leading translational NK cell program at DFCI evaluating memory-like NK cells in combination with novel immune-modulatory agents in patients with advanced malignancies including AML and MDS relapsed after stem cell transplantation, MRD+ multiple myeloma (in combination with CD38 ARM) and head and neck cancer (in combination with CTLA-4 blockade/ipilimumab and IL-15 super-agonist).

Volker Huppert

Chief Development Officer Glycostem Therapeutics

Volker Huppert is a graduate bioprocess engineer from RWTH Aachen University. Among his achievements are participation in the set up of a quality system for a medical device/biotechnology company and development of several clinical-level reagents, disposable tubing sets and process software for cell separation and cell culture medical devices. He contributed to both the tubing set and process software development of a leading cell therapy-manufacturing device. Additionally, he managed projects and teams developing cell-manufacturing procedures for hematopoietic stem cells and Natural Killer cells. Volker has published 12 papers in peer reviewed journals over the past 20 years while working for a leading biotechnology company and is co-inventor of 9 patent families, including methods for T cell depletion of hematopoietic stem cell products, NK-cell transduction and NK-cell proliferation.

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SPEAKERS

Nina Möker

R&D Reagents Manager, Allogeneic Cell Therapy, Miltenyi Biotec

Evelyn Ullrich MD

Arbeitsgruppe Zelluläre Immunologie, Universitätsklinikum, Frankfurt am Main (kgu.de)

Rizwan Romee MD

Associate Professor of Medicine, Harvard Medical School, Dana Farber Cancer Institute

Volker Huppert

Chief Development Officer Glycostem Therapeutics

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