GlycoStem is a clinical-stage biotechnology company creating cellular immunotherapies to combat cancer. Its main pursuit involves using Natural Killer (NK) cells derived from the stem cells found in umbilical cord blood. The company’s goal is to harness the potential of these immune cells to develop standardized treatments that are readily available for patients.
The company’s lead product, oNKord®, is being developed as an “off-the-shelf” treatment. This signifies a shift from personalized therapies that must be created for each person. Instead, GlycoStem aims to provide a more accessible and cost-effective option for cancer care. The company has focused its efforts on hematological cancers and solid tumors.
The Role of Natural Killer Cells in the Body
Natural Killer (NK) cells are a type of white blood cell that forms a part of the body’s innate immune system, which provides immediate defense against threats. Unlike other immune cells, such as T-cells, NK cells do not need prior exposure to a pathogen or abnormal cell to be activated. Their primary job is to patrol the body, identifying and destroying cells that are stressed, infected by viruses, or cancerous.
NK cells identify problematic cells through a “missing-self” mechanism. Healthy cells present Major Histocompatibility Complex (MHC) class I molecules on their surface, signaling to NK cells that the cell is healthy. When a cell becomes cancerous or infected, it often stops presenting these MHC proteins, which alerts the NK cell to the problem.
NK cells also recognize target cells by detecting stress-induced ligands. When cells are under duress, they display certain molecules on their surface that are not normally present. NK cells have receptors that bind to these stress ligands, which acts as an activation signal prompting the NK cell to eliminate the compromised cell.
Once an NK cell identifies a target, it releases cytotoxic granules containing proteins like perforin and granzymes. Perforin creates pores in the target cell’s membrane, allowing granzymes to enter. Inside the target cell, granzymes trigger a process of programmed cell death known as apoptosis, effectively eliminating the threat without causing widespread inflammation.
Manufacturing Cellular Immunotherapy
The production of GlycoStem’s therapeutic product, oNKord®, begins with hematopoietic stem cells sourced from donated umbilical cord blood. Umbilical cord blood is a rich source of these potent stem cells, which can develop into various types of blood and immune cells. This provides an ethically sourced and readily available material for the therapy.
These sourced stem cells then undergo ex vivo expansion and differentiation in a controlled laboratory environment. GlycoStem uses a proprietary platform to culture these stem cells, encouraging them to multiply and mature specifically into functional NK cells. This process is designed to generate a large, pure population of NK cells from a single umbilical cord blood unit.
The ability to produce vast quantities of NK cells from a single donor unit enables the creation of an allogeneic product. This means a single batch can be used to treat multiple individuals, making the treatment more accessible.
The final product is a cryopreserved formulation containing a high concentration of these active NK cells. This allows the therapy to be stored for extended periods and shipped to clinical sites globally. The goal of this manufacturing pipeline is to create a standardized, consistent, and potent cellular immunotherapy that can be administered to patients without the logistical delays associated with autologous (patient-derived) therapies.
Mechanism of Action in Cancer Treatment
When GlycoStem’s manufactured NK cells are infused into a patient, they are designed to immediately seek out and destroy cancer cells. Because the therapy is “off-the-shelf,” treatment can begin without the delay required for patient-specific manufacturing. These laboratory-grown NK cells, which make up the product oNKord®, function with heightened potency compared to the body’s naturally circulating NK cells. They are prepared to overcome some of the tactics that tumors use to evade the native immune system.
The primary mechanism of action involves targeted cytotoxicity. Upon encountering a tumor cell, the infused NK cells release cytotoxic granules containing perforin and granzymes. These proteins work together to trigger apoptosis, or programmed cell death, in the malignant cell.
This therapeutic application is a more concentrated and directed version of the natural NK cell function. While the body’s own NK cells perform continuous surveillance, their numbers can be insufficient to control aggressive cancers. GlycoStem’s therapy provides a large, highly active population of NK cells intended to overwhelm and eliminate the malignancy.
Clinical Development and Targeted Diseases
GlycoStem is advancing its NK cell therapy through clinical trials to evaluate its safety and effectiveness. The primary diseases targeted are hematological malignancies, with a focus on Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM). These cancers of the blood and bone marrow are suitable targets for this immunotherapy.
AML and MM were selected as initial indications because malignant cells in these cancers are more accessible to intravenously infused therapies compared to solid tumors. Clinical trials in this area aim to determine the optimal dosage, confirm the therapy’s safety profile, and gather data on its ability to control the cancer.
The clinical development for oNKord® is proceeding through phased trials, including a Phase I/IIa study known as the WiNK trial for AML patients. These studies monitor for treatment response, such as achieving measurable residual disease (MRD) negativity, an indicator of longer-term survival. The therapy has received Orphan Drug Designation from the FDA and EMA for AML, and from the FDA for Multiple Myeloma, to facilitate its development.
Data on patient outcomes and safety from these early-phase trials is used to refine treatment protocols and inform the design of larger, later-stage trials. The goal of this clinical development process is to establish oNKord® as a standard-of-care treatment option for these challenging cancers.