From Ideas to Impact

Pelotonia’s impact is perhaps most obvious in discoveries made and published in scientific journals by teams of researchers who have received Pelotonia support over the past few years. Some examples:

Form of Immune Therapy Might Be Effective for Multiple Myeloma

A study by researchers at the OSUCCC – James provided evidence that genetically modifying immune cells may effectively treat multiple myeloma, a disease that will account for an estimated 24,000 new cases and 11,100 deaths in 2014. The researchers, supported by a Pelotonia Idea Grant, modified a type of human immune cell called T cells to target a molecule called CS1, which is found on more than 95 percent of myeloma cells, and to kill those cells. They grew the modified cells in the lab to increase their numbers and injected them into an animal model, where they again killed human myeloma cells. The findings were published in the journal Clinical Cancer Research. “Despite current drugs and use of bone marrow transplantation, multiple myeloma is still incurable, and almost all patients eventually relapse,” says co-principal investigator Craig Hofmeister, MD, MPH. “This study presents a novel strategy for treating multiple myeloma, and we hope to bring it to patients as part of a phase I clinical trial as soon as possible.” Principal Investigator Jianhua Yu, PhD, says the study “shows that we can modify T cells to target CS1, and that these cells efficiently destroy human multiple myeloma cells.” Yu notes that these therapeutic T cells have the potential to replicate in the body and therefore might suppress tumor growth and prevent relapse for a prolonged period.

AML Score That Combines Genetic and Epigenetic Changes May Help Guide Therapy

Currently, doctors use chromosome markers and gene mutations to determine the best treatment for patients with acute myeloid leukemia (AML). But a study at the OSUCCC – James suggests that a score based on seven mutated genes and the epigenetic changes that the researchers discovered were present might help guide treatment by identifying novel subsets of patients. The findings, published in the Journal of Clinical Oncology, come from a study supported in part by funds from the Pelotonia Fellowship Program. Overall, the findings suggest that patients with a low score – indicating that one or none of the seven genes is overexpressed (too active) in AML cells – had the best outcomes, and that patients with high scores – that is, with six or seven genes highly expressed – had the poorest outcomes. “To date, disease classification and prognostication for AML patients have been based largely on chromosomal and genetic markers,” says principal investigator Clara D. Bloomfield, MD, a Distinguished University Professor at Ohio State and senior adviser to the OSUCCC – James. “Epigenetic changes that affect gene expression have not been considered. Here, we show that epigenetic changes in previously recognized and prognostically important mutated genes can identify novel patient subgroups, which might better help guide therapy.” Guido Marcucci, MD, also of the OSUCCC – James, was first author for the study.

Cancer Gene NRAS Produces 5 Variants, Study Finds

A gene called NRAS that was discovered 30 years ago and is now known to play a fundamental role in cancer development produces five gene variants (called isoforms) rather than just the original form, a study at the OSUCCC – James showed. The study, supported by funds from the Pelotonia Fellowship Program and published in Proceedings of the National Academy of Sciences of the USA, identified four previously unknown variants that the NRAS gene produces. The finding might help improve drugs for cancers in which aberrant activation of NRAS plays a crucial role. “We believe the existence of these isoforms may be one reason why NRAS inhibitors have so far been unsuccessful,” says corresponding author Albert de la Chapelle, MD, PhD, a Distinguished University Professor at Ohio State. Cosenior author Clara D. Bloomfield, MD, also a Distinguished University Professor at Ohio State, notes that one of the newly discovered isoforms might play a greater role in the development of some cancers than the known protein itself. “The discovery of these isoforms might open a new chapter in the study of NRAS,” says first author Ann-Kathrin Eisfeld, MD, a postdoctoral fellow in the laboratories of de la Chapelle and of Bloomfield. “Knowing that they exist may lead to the development of drugs that decrease or increase the expression of one of them and provide more effective treatment for selected cancer patients.”

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