The introduction of synthetic Notch receptors specific to neuroblastoma increases the production of interferon gamma only in the presence of the neuroblastoma cells, upregulating HLA and sensitizing the cells to killing by T-cells.

HLA downregulation is one of the most common immune escape mechanisms and frequently observed in patients with high-risk neuroblastoma in whom it is associated with an adverse prognosis.

Solid tumors such as neuroblastomas are especially challenging to CAR immunotherapies because cancer-specific antigens have not been identified and current solid tumor antigens are also expressed in healthy cells causing off-target activity. Conversely, CAR immunotherapies have gained traction to combat solid tumors, as they can be tumor-specific, but have not always demonstrated strong efficacy and success in clinical trials. University of Utah researchers have developed a novel strategy that could be complementary to CAR therapies or a stand-alone treatment for solid tumors. The technology involves restoring the loss of HLA in neuroblastomas through selectively targeting tumor cells and activating the interferon gamma pathway (INFG), a cytokine involved in MHC-II response. Utilizing engineered T-cell lines that confer recognition of GD2 antigens and exploit INFG activation, co-culture of these T-cells with various cancer cell lines repress cancer cell proliferation.

Optimization & Testing

• Enable the immune system to mount an attack on solid tumor cancer cells with less off-target effects
• Less immunogenicity than current CAR-T technologies (ie T-cell storms)
• Less likely to have relapse than CAR-T technologies

Fiorella Iglesias, Siani Weston, Djordje Atanackovic, Tim Luetkens. Enhancement of anti-tumor immunity by the adoptive transfer of T cells engineered to restore HLA expression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2171.

https://patents.google.com/patent/US20220411535A1/

Aaron Duffy
(801) 585-1377
aaron.duffy@utah.edu