Researchers Making Leukemia Cells Kill Each Other

AScientists at The Scripps Research Institute (TSRI) have found a way to change leukemia cells into leukemia-killing immune cells. The surprise finding could lead to a powerful new therapy for leukemia and possibly other cancers.

"It's a totally new approach to cancer, and we're working to test it in human patients as soon as possible," said senior investigator Richard A. Lerner, Institute Professor and the Lita Annenberg Hazen Professor of Immunochemistry at TSRI.

The findings, published this week in the Proceedings of the National Academy of Sciences, result from the discovery of a rare human antibody.

Unexpected Effects

The Lerner laboratory has pioneered techniques to generate and screen very large libraries of antibodies (immune system molecules), using the power of large numbers to find therapeutic antibodies that bind to a desired target or activate a desired receptor on cells.

Recently, the lab mounted an effort to find therapies for people with certain immune cell or blood factor deficiencies, by looking for antibodies that activate growth-factor receptors on immature bone marrow cells that might induce these bone marrow cells to mature into specific blood cell types. Over the past few years, Lerner and his team succeeded in identifying a number of antibodies that activate marrow-cell receptors in this way.

Transformation

In the new study, Richard A. Lerner, institute professor and the Lita Annenberg Hazen professor of Immunochemistry at TSRI and senior investigator, teamed up with colleagues, including first author Kyungmoo Yea, an assistant professor of cellular and molecular biology at TSRI. They decided to test 20 of the recently discovered receptor-activating antibodies on acute myeloid leukemia cells taken from human patients. One of the antibodies ended up having an incredible impact on the leukemia cells.

(A) Normal BM CD34+ cells and AML cells after 4 d culture in the presence of PBS, antibody (10 μg/mL), or TPO (10 ng/mL). The red arrow indicates a megakaryocyte. The red-boxed Inset shows an enlarged image of a differentiated cell. (B) The AML cells after 4 d culture with various concentrations of antibody

PNAS - Agonist antibody that induces human malignant cells to kill one another

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