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Siteman fund awards $900,000 for novel blood cancer treatment

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A unique approach to treating lymphoma and leukemia has received a two-year, $900,000 grant from the Alvin J. Siteman Cancer Research Fund.

At the heart of the new therapy are the immune system’s T cells, which typically fight off disease. In cancer patients, T cells lose the ability to recognize and attack cancer cells. The therapy involves genetically altering – or supercharging – T cells to home in on cancer cells and destroy them. These modified T cells have been dubbed CAR-T cells, which stands for chimeric antigen receptor T cells.

technician in a CAR-T Cell manufacturing lab
CAR-T Cell manufacturing

An approach developed by John F. DiPersio, MD, PhD, the Virginia E. and Samuel J. Golman Endowed Professor of Medicine and director of the Division of Oncology at Washington University School of Medicine and deputy director of Siteman Cancer Center, differs from other CAR-T cell therapy methods. Those methods rely on harvesting and re-engineering a patient’s own T cells, which is challenging because normal T cells and cancerous T cells look very similar. Their similarity can lead to the unwanted self-killing of CAR-T cells before they can be therapeutically effective. Also, it’s expensive to harvest enough of a patient’s own T cells without contamination by cancerous cells. An alternative — using a healthy donor to supply the CAR-T cells — may cause life-threatening graft-versus-host disease in patients.

John DiPersio, MD, PhD
John DiPersio, MD, PhD

In response to these challenges, DiPersio and his team have developed a CAR-T cell that could be mass-produced at less expense to target specific T-cell malignancies. DiPersio believes their CAR-T cell represents a new and promising treatment for T-cell acute lymphoblastic leukemia (T-ALL) and non-Hodgkin’s T-cell lymphoma. Through gene editing, these cells look different from the cancerous T cells, so they are spared from self-killing. These cells also are able to kill cancerous T cells in a cell culture dish and in mice without causing graft-versus-host disease. This approach does not require the T-cell donor to be related to the patient or have similar immune system characteristics. Anyone can serve as a T-cell donor because the cells are processed — using the gene editing technology CRISPR — to remove the machinery that triggers graft-versus-host disease. The cells are further edited to include machinery that specifically homes in on the cancer.

With support from the Alvin J. Siteman Cancer Research Fund, DiPersio’s team, led by Matthew L. Cooper, PhD, an instructor in medicine, will do work that will allow this new therapy to move into the clinic as the first-in-people targeted CAR-T therapy for patients with relapsed T-cell hematologic malignancies. Support for the preclinical lab work leading to the first clinical trial was provided by the Children’s Discovery Institute.

The Siteman Cancer Research fund aims to advance promising early stage science that because of its unconventional approach might not receive funding from traditional sources. Proposals are reviewed by experts not affiliated with Siteman Cancer Center or Washington University School of Medicine.

Alvin J. Siteman, an emeritus Washington University trustee, chairman of Site Oil Co. and president of Flash Oil Co., established the Siteman Cancer Research Fund in 2010. Since then, the fund has provided $9.6 million in funding to 15 projects at Washington University/Siteman Cancer Center.

 

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