EXTH-77. EXTENDED HALF-LIFE IL-2 SYNERGIZES WITH Α-PD-1 FOR TREATMENT OF PRECLINICAL MURINE GLIOBLASTOMA MODELS

• DOI: 10.1093/neuonc/noad179.0930
• Publication Date: 2023-11-11T23:15:30Z
• Authors: Carley Owens; Zachariah Tritz; Katayoun Ayasoufi; Delaney Wolf; Ian Parney; Michael Hanson; Jin Fang; Aaron Johnson; Jian Campian; Cori Fain; Benjamin Himes; Courtney Malo; Emma Goddery; Lila Yokanovich; Chensu Wang; Richard Vile; Kelly Moynihan; Darrell J Irvine; Rosa Mercano; Dane Wittrup; Mark Maynes
• Keywords: Immune checkpoint; Combination therapy

Abstract α-PD-1 checkpoint blockade is a promising immunotherapeutic approach for many solid tumors; however, this strategy minimally effective GBM patients as monotherapy. One potential reason why ineffective the tumor microenvironment and systemic derangements of immune system which are prevalent in patients. We have successfully modeled peripheral experimental murine models. These include low blood CD4 T cell counts, reduced MHC class II expression on monocytes, atrophy primary organs animals harboring gliomas. therefore hypothesized that extended half-life IL-2, potent cytokine promotes proliferation, differentiation, killing activity cells, could overcome potentially synergize with therapy. In cohorts C57Bl/6 mice, we supplemented multiple bio-engineered IL-2 molecules to treat GL261 CT2A orthotopic glioma models normally resistant observe statistically significant increase survival GL261-bearing receiving combination reagents αPD-1 therapy relative control-treated mice. Some had reduction burden levels below detection. long-term survivors underwent rechallenge experiment second inoculation GL261-Luc effectively cleared without further therapeutic intervention. This intervention causes shift profile, including formation mature responses, well restoring diminished counts animals. Finally, combining independently CD8 response. Together, these data suggest immunotherapies employing fusion proteins translational clinic do not require identification specific antigens efficacy