WASHINGTON, D.C.—Biotech newcomer GT Biopharma recently revealed promising results utilizing their proprietary Tri-specific Killer Cells (TriKEs) to treat acute myeloid leukemia (AML). Data presented at the American Society of Hematology (ASH) Annual Meeting demonstrate that their TriKE cells, when bolstered by the additional of the cytokine IL-15, show promising clinical potential for the treatment of AML, as well as myelodysplastic syndromes (MDS) and mastocytosis. The preclinical findings have resulted in FDA approval to conduct a first-in-human, first-in-class Phase 1 clinical trial, which will commence in the first half of this year.
GT Biopharma emerged in 2017 following a series of mergers and acquisition of Oxis International. The company has an exclusive partnership with Dr. Jeffrey Miller, deputy director of the University of Minnesota’s Masonic Cancer Center, in the ongoing refinement of the process. The relationship with Miller and his team offers what GT Biotech sees as a significant strategic advantage.
“We continue to be encouraged by the data from our TriKE program, [which is] being conducted by leading NK cell experts at the University of Minnesota. These findings have supported us with the confidence to proceed with our first-in-class TriKE Phase 1 study,” commented Dr. Raymond Urbanski, CEO of GT Biopharma. “We are grateful to renowned NK cell expert, Jeffrey Miller ... and his team, and look forward to providing further updates as we continue to advance what we believe to be a potentially revolutionary product candidate.”
According to Miller, “These studies demonstrate the adaptability of the TriKE platform to optimize TriKE constructs and candidate selection in order to address unmet medical needs. We continue to work with our partners at GT Biopharma in moving the TriKE platform forward.”
While T cell therapies have proliferated over the last two decades, their success as an immunotherapy has been tempered by challenges in refining dosing levels and in significant instances of post-treatment toxicity for the patient. Miller first identified natural killer (NK) cells in 1994 as a means to engage one’s own immune system to fight cancer, and has been working to refine their use ever since. He understood that NK cells would kill cells they could identify as foreign, but, of course, cancer is outstanding at mimicking one’s own cells, thus tricking the NK cells. By adding the IL-2 phytokine, creating a bispecific killer cell, he was able to induce activation of the NK cells, but cancer could still evade the immune response. He continued with the addition of IL-15, a cytokine that induces cell proliferation, thus making a TriKE. Lastly, the addition of CD33 ensured that the specific AML cancer cell was targeted and killed by the NK cells.
“GT Biopharma utilizes the NK stimulating cytokine human IL-15 as a crosslinker between two scFvs, which is designed to provide a self-sustaining signal leading to the proliferation and activation of NK cells thus enhancing their ability to kill cancer cells mediated by antibody-dependent cell-mediated cytotoxicity (ADCC),” explains Urbanski.
According to Urbanski, once the proof of concept is established in the clinical trial, NK-based technology can potentially be applied to fight countless diseases. It will be possible to program the NK cells to attack any malignancy, including solid tumors, hematological diseases and even autoimmune disorders such as lupus and HIV.
Clinical trials should be starting by June 2019. The challenge will be modulating the dosage to maximize efficacy without triggering the known toxic responses to IL-15, which include hypotension, tachycardia and fever. The goal will be to locate the optimal biologically effective dose to move in to Phase 2 testing, and then expand the technology from there.
“The depth and breadth of where we can take this technology is only limited by the imagination,” asserts Urbanski. “This technology will be a game-changer for targeting and treating liquid and solid tumors. We are looking at a therapy to be reckoned with.”