Emmet Mc Cormack

Emmet Mc Cormack (Ireland) received a double honors degree in mathematics and chemistry from DIT and TCD, Ireland (1994-98), before pursuing a PhD in Pharmacognosy at the School of Pharmacy, TCD, where he designed, synthesized, and characterized the biological efficacy of novel dual antimitotic/aminopeptidase N molecules. Subsequently, Mc Cormack took a researcher position at the lab of Professor Bjørn Tore Gjertsen (2002), shifting fields to preclinical modeling and molecular imaging. In 2008, Mc Cormack and Gjertsen founded KinN Therapeutics AS. Mc Cormack was awarded TMF funding to start his own research group, founding PreCOS in 2011. In 2013, Mc Cormack was made Professor of Pharmaceutics. More recently, he has a 20% researcher position at Haukeland University Hospital, is associated PI at NCMM, CanCELL SFF, and has served as head of innovation (2017–2021), and periodically, vice-head of department (2018–2020) at the Department of Clinical Science, UiB, head of the preclinical facilities at UiB (2020–2022) and is working group 2 leader of the COST action “Immunomodel”.

Brief group presentation and history

PreCOS was founded in 2011, and together with Professor Line Bjørge, Mc Cormack founded INOvA in 2016. The current dogma of rushing novel pharmaceuticals through inappropriate preclinical models is one of the major reasons for the limited clinical penetration of novel drugs. Despite this, the preclinical step in drug development is generally overlooked and models are chosen to fit the desired result, rather than using them as valuable tools to drive clinical development.

Research focus

The group’s core activities focus on the development, characterization, and application of clinically relevant models (patient-derived xenografts (PDX), Hu-PDX, in vitro decellularized scaffold platforms) and multimodal molecular imaging strategies and how they believe judicious application of these technologies can expedite clinical development of novel therapeutics. More recently, the group has focused on the development of novel immunotherapies (CAR-T and BiTes).

Subprojects

SonoCURE: This project explored the application of sonoporation in the treatment of PDAC. The application aimed to preclinically elucidate, evaluate, and potentiate a new era of sonoporation theranostics for PDAC through the application of innovative biomarker mining, organoid models and preclinical modeling. This work provided the preclinical platform (Kotopoulis et al., Mol. Imaging Biol. 2014) for the world’s first clinical trial in sonoporation (Dimcevski et al., J. Controlled Release 2016). Furthermore, a novel decellularized porcine tissue platform was developed for PDAC and ovarian cancer (Helgestad Gjerde et al., manuscript 2024.)

Novel Models and Therapeutic options for Haematological Malignancies: This work elucidated a novel Axl isoform, Axl3, and demonstrated the application of Axl inhibition as a novel therapeutic strategy in mantle cell lymphoma (Gelebart et al., Blood 2023). Additionally, Li et al., Cell Stem Cell 2014 elucidated a novel therapeutic strategy targeting leukemic stem cells’ expression of the biomarker FLT3 ITD. Lee et al., PNAS 2012 and subsequently, Shafiee, et al., Br. J Haematol. 2021 described novel scaffold-derived hematopoiesis and MDS models, respectively.

ISPIC: PreCOS and INOvA received 3 ESRs as part of this consortium, with UiB’s mandate to develop novel immunocompetent models of cancer, develop FGS to aim surgical resection in addition to high-dimensional analysis of HGSOC. Kleinmanns et al., ebiomedicine 2020 are two works based on the use of the biomarker CD24 to noninvasively image HGSOC and application in fluorescence image-guided surgery (FGS) to increase tumor debulking.

Furthermore, Kleinmanns et al., Cancers 2022 describes the development of an innovative model of orthotopic HGSOC complete with human immune system, characterized by high-dimensional CyTOF analysis and used to evaluate the use of immunotherapeutics.

IDDEA: In collaboration with OUS (Sébastien Wälchli), the project aims to generate and evaluate novel CAR-T. To date, the project has resulted in two high-impact publications. Casey et al., J. Immunother. Cancer 2024 details the development and implantation of MUC16 targeted CAR-T, while Caulier et al., Cell Rep Med 2024 describes the identification of CD37 as a novel therapeutic target in AML and the successful targeting of a preclinical development of a novel CD37 CAR-T.

Translational, clinical, and societal importance

The finding that sonoporation impacted the growth of PDAC in preclinical models was successfully translated to the clinic, resulting in a major improvement of clinical outcome (17.6 vs. 8.8 months). KinN Therapeutics AS’ preclinical collaboration with Celegene (now BMS) on the compound CC90009 resulted in a clinical trial and one cure (to date) for a patient with AML. Preclinical development of vididencel by scientists at PreCOS and KinN Therapeutics AS led to a clinical trial of this DC based vaccine by Mendus AB. Currently, vididencel has reached phase II. The Mc Cormack group was the first to demonstrate the preclinical activity of tebentafusp, a bi-specific gp100 targeted T cell receptor protein (KIMMTRAKTM; Mc Cormack et al., Cancer Immunol. Immunother. 2012) in collaboration with Immunocore. KIMMTRAK is now approved for HLA-A*02:01–positive metastatic or unresectable uveal melanoma. Fosse et al., BMC Med. 2023 outlines recommendations for robust and reproducible preclinical research in personalized medicine and is anticipated to increase the impact of preclinical research.

Future perspectives from 2024

Ideally, the Mc Cormack group would welcome an SFI grant to continue the great work started at CCBIO.