Dr. Weichert receives NCI P01 grant for advanced cancer research

Posted on October 2020

Dr. Jamey Weichert, faculty member of the UW Department of Radiology in the Imaging Sciences Section, and Director of the Contrast Agent Development Laboratory, recently received a $12.5 million dollar, five-year NCI PO1 grant from the National Institutes of Health. Dr. Weichert’s research is focused on the development of new cancer imaging and therapy agents. The lab uses known biochemistry pathways to design molecules that selectively target cancer cells and cancer stem cells.

This specific grant is for Dr. Weichert’s project entitled “Molecular Targeted Radionuclide Therapy for Tumor Immunomodulation and Enhancing Immunotherapy Response.” Dr. Weichert and Zachary Morris, MD, PHD, Assistant Professor in the Department of Human Oncology serve as co-principal investigators of the multi-disciplinary grant which studies the impact of combining targeted radionuclide therapy (TRT) with immunotherapies on tumor microenvironment with the goal of stimulating the immune system to recognize and kill cancer cells as well as induce T-cell immunity against the target cancer.

“Preclinical results thus far suggest a high cure rate is feasible in several different tumor types,” said Dr. Weichert. “Our hope is to show that low radiation doses of TRT can enable the ability of the immune system to recognize and kill tumor cells systemically while also inducing T cell memory specific to solid cancers.”

Developed in the Weichert lab, NM600, a third-generation tumor-selective alkylphosphocholine (APC) chelate capable of selectively delivering a variety of imaging and therapy metal isotopes to a variety of tumor types, is utilized as the TRT agent which is capable of delivering relatively low radiation doses found to be necessary for immuno-stimulation in a variety of tumor types regardless of anatomic location, including the brain. Other theranostic agents currently used in the clinic or in late stage trials will also be combined with immunotherapy. TRT agents will be radiolabeled with beta- and alpha-emitters to study the relative efficacy of using different types of radiation as well.

The grant combines 4 projects with 3 new core facilities. The projects include new TRT agents (Drs. Weichert and Morris) used in combination with three prominent immunotherapy approaches including immune checkpoint inhibitors (Drs. Morris and Weichert)  immunocytokines (Drs. Sondel and Morris) and DNA-based prostate cancer vaccines (Drs. Doug McNeel and Weichert). Three core labs will support these studies including a isotope production and radiochemistry core lead by Jon Engle and Reinier Hernandez (Medical Physics and Radiology), a new advanced dosimetry core lead by Bryan Bednarz and Joe Grudzinski (Medical Physics and Radiology) and biostats core lead by KyungMann Kim (Biostatistics).

“It appears that there is a distinct radiation dosing window of opportunity for TRT to modulate tumor cell immune response,” Dr. Weichert said. “We have found that using advanced PET or SPECT imaging of the TRT agent is necessary for accurate and personalized TRT dose determination. Rodent findings will be translated into companion canine cancer patients at the UW School of Veterinary Medicine in collaboration with Dr. David Vail,” Dr. Weichert said.

The grant is accompanied by a generous $2.1M institutional match being provided from the Chancellor’s Office, Carbone Cancer Center, School of Medicine and Public Health, and the Departments of Radiology, Human Oncology, and Medical Physics.

“I was told by the NCI that this is the first ever TRT-based P01 grant – and it is very rare to get them approved on the first try,” Weichert said. “My lab’s total extramural grant support currently totals $19.2M, all of which is focused on TRT immune modulation. The PO1 also funds a new Advanced Dosimetry Core as well as a new Radiochemistry Core, both of which will eventually support our departmental clinical theranostics initiative” Weichert continued. “It all started with a UW2020 grant ($500K) in 2016 which has since spawned over $30M in follow-on funding! A huge strength of our application was the amazingly strong collaborative team which provides exceptional expertise in immunotherapy, radiotherapy, advanced dosimetry, isotope production and radiochemistry development, and TRT agent discovery and development. Moreover the team is experienced in translating technology to clinical trial status. Very few other institutions possess this unique level of expertise and resources.”