TriKEs take a strike at HIV

University of Minnesota research team works to eradicate HIV with natural killer cells

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MINNEAPOLIS—Today, it’s been announced that a collaborative research team at the University of Minnesota (UMN) has used Tri-specific killer engagers (TriKE) to target HIV-infected cells in preclinical testing.
The team was led by Jeffrey Miller, M.D., Deputy Director of the Masonic Cancer Center, University of Minnesota, and Timothy Schacker, M.D., Vice Dean of Research at the University of Minnesota Medical School and director of the Program In HIV Medicine. The two have used their combined expertise to now find an innovative approach in the hopes of potentially curing HIV.
After years of the Miller team working with natural killer (NK) cells to target cancer, and the Schacker group researching HIV reservoirs, the two physicians have joined together to combine their efforts. The potential to use a cancer-based therapy on a disease like HIV was an opportunity the teams couldn’t pass up.
“This exciting work is the result of years of collaboration between our groups, one of the great assets of team science at UMN,” said Miller. “After years of work trying to target the immune system to fight cancer, and the Miller team learning more about HIV, we decided to work together with the Schacker group to target HIV reservoirs.”
The TriKE, which was designed and developed at the University of Minnesota, was created to bind NK cells on one end, and to target cancer cells on the other end, along with costimulation by an IL-15 cytokine linker contained between the two binding domains in the same protein. In this case, the IL-15 will be combined with CD4 T cells to potentially eliminate the HIV reservoir.
“Individuals well controlled on anti-retroviral therapy are not cured, and [they are] dependent on continuous use of their medications. The challenge in the HIV field is to target the reservoir where HIV hides in tissue CD4 T cells and to destroy those sanctuary sites,” Schacker noted. “If successful, this has the potential to contribute to a cure for HIV.”
Next steps for the research group will be to optimize the TriKE constructs, followed by in vitro testing, and then moving to in vivo. If all goes as planned in that phase, the team will begin to prepare for clinical trials.
Additionally, on April 25 GT Biopharma, Inc., announced its plans to broadcast an update to shareholders and press of its proprietary TriKE for HIV infected cells and TriKE product candidate GTB-3550 developed for the treatment of acute myeloid leukemia (AML) at the University of Minnesota. The update, hosted by Miller and Schacker, will be broadcast on May 7 at 4:00 PM ET.
In preclinical testing led by Miller and Schacker, the research team designed a series of Bi- and Tri- Specific killer-engager (BiKE and TriKE) constructs to direct Natural Killer cell antibody dependent cell-mediated cytotoxicity against an HIV infected target.
The data demonstrate that a (BiKE) construct containing the Fab of an HIV bnAb and an anti-CD16 component can eliminate HIV-infected targets that express the HIV envelope on their their surface. Based on the success of the BiKE data, GT Biopharma has now expanded the BiKE's capabilities to be included in the TriKE platform, which the company believes will have further abilities to extend the cytolytic activity currently being demonstrated in its BiKE.
Anthony Cataldo, CEO of GT Biopharma stated, “There has been significant interest in the TriKE’s capabilities in HIV and oncology. This event will allow our shareholders and the press to understand the capabilities of our TriKe platform technology from the inventors perspective. We will announce more details of this upcoming event soon.”

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