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People with the blood cancer multiple myeloma can live for years in good health after treatment. But the cancer almost always comes back and is ultimately fatal for most patients.
Dr. Geoffrey Hill of Fred Hutchinson Cancer Research Center wants to change that. He hopes that a large, newly funded research project — built on unexpected discoveries his team made last year — will help him achieve his goal.
With the new project, Hill’s team will develop new immunotherapy approaches they anticipate will boost the cancer-killing, immune-stimulating power of autologous bone marrow transplantation, a longtime standard of care for myeloma. (In an autologous transplant, a patient typically receives a high dose of chemotherapy, followed by their own pre-collected blood-forming stem cells to re-establish normal blood and immune function.)
By the end of the five-year project, Hill plans to translate the new approach he develops into clinical trials for myeloma patients.
“We are developing new immunotherapy approaches after autologous transplantation with the aim of improving long-term control of myeloma,” said Hill, who is the scientific director of the Immunotherapy Integrated Research Center and holds the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research at Fred Hutch.
Most exciting to him, he said, is that the approaches the team develops “may allow autologous transplant to be curative.”
The project is funded with a new five-year, $4 million grant from the National Cancer Institute. The grant was made possible through an NCI funding opportunity associated with the Beau Biden Cancer Moonshot Initiative and is intended to accelerate bench-to-bedside research on new cancer immunotherapies. Such therapies, which harness the power of the immune system to kill cancer, are a scientific priority identified in the Cancer Moonshot Blue Ribbon Panel’s 2016 report.
Discovering, harnessing autologous transplant’s immune-stimulating powers
The rationale for the new project was established in a pair of scientific papers Hill published in 2018. In that work, Hill and teammates described how autologous transplantation stimulates patients’ immune cells to attack their cancers. The finding upturned the conventional understanding that it’s the chemotherapy part of the procedure that’s responsible for controlling the myeloma. (Read the 2018 Fred Hutch News Service story on Hill’s discovery that autologous transplantation is a form of immunotherapy.)
Based on that work, his team is designing immune-boosting combination therapies “to preserve anti-myeloma immunity pre-transplant, and boost this immunity after transplant to provide long-term immunological disease control,” Hill explained.
Specifically, Hill will develop new therapies that help keep immune cells called T cells active in their fight against myeloma. His previous research had demonstrated that myeloma came back after autologous transplantation because T cells that had been stimulated by the transplantation process became too exhausted to attack the cancer any longer.
Hill’s new project includes human and mouse studies that integrate immunology, genomics, bioinformatics and clinical oncology approaches in collaboration with scientific colleagues throughout the Fred Hutch/University of Washington Cancer Consortium.
Via this integrated team approach, Hill said, “The impact of this work will be to optimize innovative, combinational immunotherapy strategies for myeloma that will permit rapid translation into the clinic.”
