Abstract B120: Enzyme-laden microcapsules for controlled starvation of tumors
Makayla Allsberry, Lauren Bohall, Hélène Gros, Utsav Joshi, Thomas Molley, Himangshu Sonowal, Rebekah WhiteAbstract
Introduction:
A conserved feature of most solid tumors is aberrant metabolism and vascularization, which disrupt oxygen regulation and cellular glycolysis. Strategies to control tumor oxygenation are being explored to improve responses to standard-of-care therapies. HypoxyCaps are microscale gas-modulating capsules that provide spatiotemporal control of oxygen tension in vitro and in vivo. We hypothesized that locally reducing glucose and oxygen in the tumor microenvironment would increase cell death and support combination with existing therapies for solid tumors. In this study we investigated the stability and anti-tumor activity of a novel glucose oxidase (GOx) enzyme-loaded gelatin microgel capsule (HypoxyCaps) in pancreatic ductal adenocarcinoma (PDAC) models in vitro and in vivo.
Methods:
In vitro cell viability was measured using a CCK-8 assay in human (PANC-1, 79E) and murine (KPC46, KPC1199, KPC4580) PDAC cells. HIF-1α expression was analyzed by immunofluorescence. Subcutaneous tumors were established by injecting 25,000 murine KPC cells into both flanks of 6–8-week-old male C57BL/6J mice. Once tumors were palpable, mice received once weekly intratumoral HypoxyCaps treatments for 2 weeks, with tumor growth monitored twice weekly. Harvested tumors were analyzed by immunohistochemistry and flow cytometry.
Results:
HypoxyCaps retained 50% enzyme activity in ex-vivo human plasma for five days. After 48 h treatment, a concentration-dependent reduction in cell viability across all tested cell lines was observed. A 1:100 dilution of 100 U of glucose oxidase (GOx) enzyme containing HypoxyCaps led to 80-90 % decrease in cell viability. Nuclear translocation of HIF-1α was observed in HypoxyCaps treated cells. In subcutaneous murine syngeneic PDAC models, HypoxyCaps inhibited tumor growth by ∼40% without injection-site toxicity and with increased intratumoral CD45+ hematopoietic and CD8+ effector T cells.
Conclusions:
HypoxyCaps are stable and inhibit PDAC cell proliferation in vitro and in vivo. By disrupting tumor oxygen and glucose levels, they induce cancer cell death and offer strong potential for synergy with existing systemic and locoregional therapies. Ongoing studies are evaluating their effects on the tumor–immune microenvironment and in combination with approved therapeutics in murine PDAC models.
Citation Format:
Makayla Allsberry, Lauren Bohall, Hélène Gros, Utsav Joshi, Thomas Molley, Himangshu Sonowal, Rebekah White. Enzyme-laden microcapsules for controlled starvation of tumors [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B120.