WEST LAFAYETTE, Ind. \u2014 Purdue University researchers are developing innovative antibody-based immunotherapies that recruit and improve the function of the body\u2019s innate immune system to treat glioblastoma, an incurable brain tumor.<\/p>\n\n\n\n
Sandro Matosevic<\/a>\u2019s patent-pending work improves upon traditional molecules to recruit and activate natural killer (NK) cells. NK cells are a type of white blood cell that have granules with enzymes to kill tumor cells or virus-infected cells. Matosevic is an associate professor in the Department of Industrial and Molecular Pharmaceutics<\/a> in Purdue\u2019s College of Pharmacy<\/a> and on the faculty of the Purdue Institute for Cancer Research<\/a> and Purdue Institute for Drug Discovery<\/a>.<\/p>\n\n\n\n \u201cTraditional NK cell engagers, or NKCEs, are antibody-like molecules that bring NK cells and cancer cells in close contact. This stimulates the immune cell to kill the cancer,\u201d he said. \u201cThe engagers capitalize on the innate capabilities of NK cells, but NK cells lack efficacy and specificity against glioblastoma and the ability to deeply infiltrate the tumor.\u201d<\/p>\n\n\n\n Unlike traditional NKCEs, Matosevic\u2019s technology recruits immune cells to improve their homing to the tumor and, as an additional function, tethers them to cancer cells. This leads to a significant improvement in efficacy against tumors and a comparative reduction in tumor cell resistance.<\/p>\n\n\n\n \u201cOur NKCEs can be readily manufactured using known reagents and administered off the shelf to patients alongside autologous or allogeneic cell-based products without limitations on clinical use,\u201d Matosevic said.<\/p>\n\n\n\n Matosevic disclosed the innovation to the Purdue Innovates Office of Technology Commercialization<\/a>, which has applied for a patent to protect the intellectual property. Industry partners interested in developing or commercializing the innovation should contact Joe Kasper, assistant director of business development and licensing \u2014 life sciences, at jrkasper@prf.org<\/a> about track code 70791.<\/p>\n\n\n\n Matosevic and his team have put the Purdue NKCEs through three critical validation tests.<\/p>\n\n\n\n \u201cFirst, we tested a number of designs to identify a lead NKCE format,\u201d Matosevic said. \u201cWe validated production of the lead engager by protein expression assays, Western blot and SDS-PAGE, followed by initial functional assessments using binding assays.\u201d<\/p>\n\n\n\n After development and production, Matosevic and his team conducted functional assessments of the NKCE.<\/p>\n\n\n\n \u201cDuring the trial, our NKCE was tested on ex vivo-expanded human NK cells and analyzed for induced cytotoxicity of NK cells against glioblastoma spheroids,\u201d he said. \u201cOur engager was found to significantly enhance the ability of NK cells to kill the spheroids.\u201d<\/p>\n\n\n\n Finally, the engager was tested in vivo in mice models.<\/p>\n\n\n\n \u201cMice that received the engager treatment survived longer, had better control of their tumors and saw superior intratumoral infiltration of NK cells,\u201d Matosevic said.<\/p>\n\n\n\n Matosevic said the next steps to develop the Purdue NKCE for glioblastoma are to complete Investigational New Drug-enabling studies, which would bring the technology to human trials. These studies are currently underway.<\/p>\n\n\n\n The development of Matosevic\u2019s technology was funded by grants from the Purdue Institute for Cancer Research, the Purdue Research Foundation, the National Institutes of Health and the V Foundation for Cancer Research.<\/p>\n\n\n\n Glioblastoma is a brain tumor for which chemotherapy, surgery and most, if not all, immunotherapies don\u2019t work. The current life expectancy after diagnosis has been at 15-18 months for the past three decades.<\/p>\n\n\n\n Matosevic said, \u201cTraditional immunotherapies fail because there are few natural therapeutic immune cells, such as NK cells, in the glioblastoma tumor. The cells that are there tend to be dysfunctional, and current therapies fail to increase their recruitment or function.\u201d<\/p>\n\n\n\n The Purdue Innovates Office of Technology Commercialization<\/a> operates one of the most comprehensive technology transfer programs among leading research universities in the U.S. Services provided by this office support the economic development initiatives of Purdue University and benefit the university\u2019s academic activities through commercializing, licensing and protecting Purdue intellectual property. In fiscal year 2024, the office reported 145 deals finalized with 224 technologies signed, 466 invention disclosures received, and 290 U.S. and international patents received. The office is managed by the Purdue Research Foundation, a private, nonprofit foundation created to advance the mission of Purdue University. Contact otcip@prf.org<\/a> for more information.<\/p>\n\n\n\n Purdue University is a public research university leading with excellence at scale. Ranked among top 10 public universities in the United States, Purdue discovers, disseminates and deploys knowledge with a quality and at a scale second to none. More than 107,000 students study at Purdue across multiple campuses, locations and modalities, including more than 58,000 at our main campus in West Lafayette and Indianapolis. Committed to affordability and accessibility, Purdue\u2019s main campus has frozen tuition 14 years in a row. See how Purdue never stops in the persistent pursuit of the next giant leap \u2014 including its comprehensive urban expansion, the Mitch Daniels School of Business, Purdue Computes and the One Health initiative \u2014 at https:\/\/www.purdue.edu\/president\/strategic-initiatives.<\/p>\n\n\nValidation tests and next steps<\/h2>\n\n\n\n
About glioblastoma<\/h2>\n\n\n\n
About Purdue Innovates Office of Technology Commercialization<\/h2>\n\n\n\n
About Purdue University<\/h2>\n\n\n\n