An approach that programs human T-cells to recognize and kill malignant B-cells has shown promise in a mouse model, according to an article in the March issue of Nature Medicine.

American researchers genetically engineered the CD19 surface receptor, which is on normal and cancerous B lymphocytes, introduced it into cultured human T-cells, and infused the T-cells into mice with widespread tumor cells. The team used positron emission tomography to locate tumors and confirm that the modified T-cells eradicated the cancers. The current work with adoptive immunotherapy involving human T-cells is the first to demonstrate tumor-killing ability in a living model.

“Our findings represent a step forward in the field of adoptive T-cell therapy,” said senior author Michel Sadelain, M.D., Ph.D. “Our studies aim to better understand the biological needs of T-cells that are targeted to tumors and may potentially be applied to a variety of cancers in the foreseeable future.”

Earlier experiments had shown that genetically modified human T-cells could kill tumor cells in laboratory culture. However, the cells could not successfully carry out other immunological responses such as maintaining cell division, and they died prematurely when they were infused into mice. In the current study, researchers overcame some of these limitations by designing a method that genetically changed the ability of human T-cells to recognize certain blood cancers and multiply in such a manner that they retain the ability to eliminate human tumors in vivo in mice.

“This unique methodology enables us to expand the number of specific T-cells to clinically relevant numbers and extend their viability, thereby enhancing their therapeutic effectiveness and enabling them to eradicate disease, in this case a B-cell tumor,” said Dr. Sadelain.

In addition, researchers were able to show that T-cells obtained from patients with advanced chronic lymphocytic leukemia could be targeted to efficiently kill their own tumor cells in laboratory culture.

“Collectively, these findings show that we have met many of the criteria necessary to conduct a clinical trial and test this approach in humans,” said lead author Renier Brentjens, M.D., Ph.D.

The American team plans a clinical trial for patients with B-cell leukemias and lymphomas such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, and most non-Hodgkin’s lymphomas.