Development and validation of orthotopic oncopig glioma models for preclinical locoregional therapeutic evaluation

The National Cancer Institute awarded SUS Clinicals Inc. $400,001 for development and validation of orthotopic oncopig glioma models for preclinical locoregional therapeutic evaluation under the Cancer Treatment Research program (CFDA 93.395) on September 1, 2026.

The project develops immunocompetent large-animal glioblastoma models using genetically engineered oncopig and human patient-derived glioma cells expressing PD-L1 and IDO fusion protein to evade immune rejection. These models enable assessment of clinically realistic neurosurgical delivery, imaging, device performance, safety, immune interactions, pharmacokinetics, pharmacodynamics, and efficacy at scale relevant to human trials—factors that cannot be fully replicated in vitro or in small animal models. Phase I work validates orthotopic tumor formation and PD-L1/IDO expression and functionality across oncopig, human, and murine glioma cells. The approach addresses limitations of immunocompromised animal xenograft models while enabling modeling of clinically observed tumor heterogeneity with defined driver mutational profiles.

The award is a Small Business Technology Transfer (STTR) Phase I grant, a mechanism that requires cooperative research between the small business recipient and research institutions, with at least 40 percent of project work performed by the small business and at least 30 percent by institutional partners. Work is performed in Chicago, Illinois. The period of performance runs September 1, 2026 through August 31, 2027.

Abstract

Glioblastoma (GBM), one of the most common and aggressive forms of brain cancer, remains incurable with a median survival rate of less than 2 years, illustrating the critical need for improved GBM treatment options. The use of surgery, radiation, and locoregional therapies for GBM treatment combined with similarities in size and drug metabolism between pigs and humans highlights the critical need for and translational value of oncopig® GBM models. Immunocompetent large-animal models are essential to evaluate clinically realistic neurosurgical delivery, imaging, and therapy-device performance within the intact brain microenvironment-factors that cannot be fully replicated in vitro or in small animal models. The translational oncopig® GBM models described in this proposal therefore provide a necessary bridge to human trials by enabling assessment of safety, immune interactions, pharmacokinetics, pharmacodynamics, and efficacy at clinically relevant scale. Importantly, there is broad interest in oncopig® preclinical trials (see support letters). This innovative fast-track sttr proposal will utilize oncopig® and human patient-derived GBM cells-genetically engineered to evade immune rejection through PD-L1 and IDO fusion protein (pido) expression-to generate immunocompetent oncopig® allo- and xenograft GBM models with defined driver mutational profiles. This approach addresses limitations of using immunocompromised/suppressed animals for PIG xenograft GBM modeling while enabling modeling of clinically observed GBM tumor heterogeneity. In phase i orthotopic tumor formation following pido+ GBM cell injection in immunocompetent swiss webster (SW) mice will be validated through the following specific aims: (1) verify pido expression and functionality in oncopig® , human, and murine GBM cells. (2) validate pido+ oncopig® , human, and murine GBM cell immune evasion and tumor formation in immunocompetent mice. Phase i will provide proof-of-concept data demonstrating orthotopic GBM formation in SW mice injected with pido+ but not pido- cells, a critical first step towards development of allo- and xenograft GBM models through injection of pido+ cells into oncopig® hosts in phase II. Criteria for transition from phase i to phase II is defined as pido+ GBM tumor development in ≥60% of allografted SW mice. In phase II the clinical relevance of oncopig® GBM models and utility for novel drug delivery studies will be demonstrated through the following specific aims: (1) characterize orthotopic oncopig® allo- and xenograft GBM models over a clinically relevant 3-month monitoring period. (2) demonstrate utility of orthotopic oncopig® GBM models for preclinical evaluation of intratumoral electrical modulation therapy. We will demonstrate that generated orthotopic oncopig® allo- and xenograft GBM tumors reflect human GBM through comparative analysis of MR imaging, histopathology, and systemic and tumor immune microenvironments. To demonstrate the utility of the oncopig® GBM model as a platform to test new therapeutic approaches, we will evaluate preclinical efficacy of a novel intratumoral electrical modulation therapy. This work will validate the relevance of orthotopic oncopig® allo- and xenograft GBM models for preclinical studies, enabling SUS clinicals to provide oncopig® GBM models and preclinical testing services to customers. Future work on expanding SUS clinicals commercialization of this technology will include pido-based modeling of other cancer types, development of additional pido+ genetically defined and patient-derived cell lines and expanding marketing efforts to the pharmaceutical sector.