Humphrey Fonge

Dr. Fonge is full professor at the Faculty of Pharmacy where he recently joined from the University of Saskatchewan, where he was full professor. Dr. Fonge completed his PhD in radiopharmacy at Katholieke Universiteit Leuven (KU Leuven) in Belgium, and postdoctoral fellowship at the University of Toronto. Additionally, he completed an MBA from the Rotman School of Business at the University of Toronto. Dr. Fonge’s education and research is centered around the development of novel biologic radiopharmaceuticals (re-named as theranostics: therapeutic and diagnostic) that are used to improve the management of different cancers. Dr. Fonge brings vast experience in nuclear medicine science and will complement the existing team at the newly installed Cyclotron Facility at the CHU de Québec-Université Laval Research Center, as well as nuclear medicine physicians and oncologists, to advance new agents to patient care.

Theranostic is a cancer management approach that allows for accurate imaging and radiotherapy in a precision medicine setting. It has recently emerged as one of the most important approaches in the management of different cancers and has seen an unprecedented increase in interest because of their potential to treat patients that have failed most other treatment options. The excellent sensitivity and specificity of diagnostic radiopharmaceuticals with positron emission tomography (PET/CT) or single photon emission computed tomography (SPECT/CT) allow for better diagnosis, staging, monitoring of response, and for the selection of patients who will benefit from the use of the paired targeted (radio)therapeutic agent. The corresponding potent (radio)therapeutic is used to achieve durable anti-tumor effects. By using many cancer-specific antibodies and peptides, the lab of Dr. Fonge has shown that radiotheranostics particularly those radiolabeled with potent alpha-emitting radionuclides such as actinium-225 have dramatic enhancements in effectiveness even in cases where traditional standards of care, which include the use of “naked” monoclonal antibodies, chemotherapeutics and antibody drug conjugates (ADCs) have failed.

The overarching research hypothesis posits that theranostics can yield greater improvements in cancer patients’ outcomes compared with conventional approaches. Additionally, these therapeutic radiopharmaceuticals can prime the tumor microenvironment and synergize with immune checkpoint inhibitors (ICI) for even more durable anti-cancer effects. The objectives of his research are :

1. To produce, process and use pharmaceutical-grade radionuclides and develop cancer specific molecular probes.
2. To develop and evaluate novel anti-cancer theranostics.
3. To study the mechanisms of immunogenic cell death caused by therapeutic radiopharmaceuticals and study their synergistic effects with immune checkpoint inhibitors (ICIs).
4.  To translate novel imaging probes and therapeutics in clinical trials.

Under objective 1, Dr Fonge’s team produces and processes pharmaceutical isotopes that are used in the development of radiopharmaceuticals. His efforts in collaboration with many other research facilities and partners have resulted in the production of important isotopes such as actinium-225, copper-67, zirconium-89 and technetium-99m. In addition, others such as gallium-68 and fluorine-18, which are routinely produced with the cyclotron are used in his research program.

Objective 2 constitutes the core research activities of Dr. Fonge and has seen the successful development of proprietary antibodies, peptides and theranostics and antibody drug conjugates (ADCs) using these compounds against many cell surface antigens that are overexpressed in most solid organ tumors. These include (but are not limited to) HER2, EGFR, Nectin-4, MUC-4, MUC-16, GPNMB, HER3, SSTR2, EpHA2/EGFR and IGF-1R. Under this objective, Dr. Fonge collaborates with clinicians and biobanks across the country to obtain patient tumor samples. These samples are used to develop mouse models to evaluate these agents.

Under Objective 3, Dr. Fonge is using multi-omic approaches to understand how radiopharmaceuticals can prime the tumor microenvironment converting it from “cold” to “hot”.  ICIs have resulted in improved outcomes for some cancers. However, only a very small fraction of patients with “immunologically hot” cancers have benefited radiopharmaceuticals. By turning “immunological cold to hot tumors”, radiopharmaceuticals can synergize with ICIs. This will pave a “new wave” of combinations of radiopharmaceutical therapeutics with ICIs as new cancer “magic bullets”. Theranostics that are show promise at improvement the management of different cancers are translated in early phase clinical trials in collaboration with a team of clinicians (oncologists, urologists, nuclear medicine physicians) under Objective 4.