Glycostem
Ushering Hope in the War against Cancer

In recent years, natural killer (NK) cell-based immunotherapy has emerged as a promising approach to combat solid tumours and haematological malignancies such as acute myeloid leukemia (AML) and multiple myeloma (MM). NK cells are innate immune cells endowed with potent cytolytic capabilities against tumours while acting as regulatory cells for the immune system. Engaging with the body’s own immune system, NK cell-based immunotherapy can boost the efficacy of anticancer therapy. With the success of developing and using immune cells as therapeutic tools, cancer immunotherapy has firmly established a new era of hope and progress in battling the disease; and, pharma companies have been quick to engineer solutions that further the cause.

Over the last decade, Glycostem has studied the role of NK cells in cancer treatments and has now developed and optimized in-house NK cell production processes. Since its founding in 2007, the Dutch organization has been focused on tapping into the potential of stem cell-derived NK cells as an asset in the fight against cancer. Glycostem successfully tested its first product, oNKord^®, which uses NK cells as a safe therapeutic agent in treatments in a phase I study published in 2017. The company, in collaboration with various partners, has also developed a second generation of Chimeric Antigen Receptor (CAR) NK cell products that enhance tumor targeting, and have fewer side effects compared to current CAR-T treatments.

Today, most healthcare facilities only have access to CAR-T cell products that have significant drawbacks. They are autologous and take 2-4 weeks to manufacture—costing valuable time that 15 per cent of cancer patients cannot afford.

Autologous products are also more expensive to manufacture since they can be used only for a single patient. Glycostem, on the other hand, can currently produce 40 CAR-NK products from umbilical cord blood units, and leaders at the company expect to improve cell yield to over 100 products in the span of two years. Additionally, the oNKord^® biobank consists of universal, off-the-shelf units that contain highly functional NK-cells with high cytotoxicity against malignant cells and can be shipped to clinical sites. By delivering off-the-shelf NK-cells, pharma companies will not have to get involved in complicated logistics, and yet, have effective treatments ready to dispatch.

Glycostem’s in-house, GMPcompliant platform is a closed-system cell culture process for the expansion of CD34+ hematopoietic stem and progenitor cells. This strategy facilitates the generation of pure, T-cell devoid products that do not rely on feeder cells. “With our platform, we can expand the original cell population by 50,000-fold without using feeder cells,” says Troels Jordansen, CEO of Glycostem. Most NK-cells manufacturers use feeder cells, leading to a higher risk of cancer DNA fragments or even cancer cells ending up in the final product. “Our technology also allows for the creation of cytotoxic NK-cells that vastly improve efficiency in treating cancer patients,” he adds. In the development of oNKord^®, Glycostem is launching unique products that help treat fragile patients for whom there are no available treatment options. These products are engineered using allogeneic materials that do not cause Cytokine Release Syndromes and are currently supplied to patient groups in clinical trials.

Cellular Immunotherapies are based on living cells, they cannot be sterilized without a total loss of potency. Glycostem’s facilities are thus designed to meet relevant regulatory health and safety requirements to ensure an utterly aseptic manufacturing process that preserves the potency and integrity of cells. Over the last three years, Glycostem has invested in state-of-the-art R&D facilities and a GMP-licensed clean room, allowing for in-house manufacturing of oNKord^® and future CAR-NK products. By November 2020, the organization will have initiated its first pivotal trial of cellular immunotherapy products. By mid2021, it will release pre-clinical data on multiple CAR-NK products, and will soon proceed to initiate phase I trials of these products in 2022.