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T-Cell Warriors—Equipped to Kill Cancer Cells

Cytotoxic T cells (blue) can be genetically reprogrammed to recognize
an antigenic marker (e.g., CD19) on a cancer cell and mount an attack
on that cell.
Cytotoxic T cells (blue) can be genetically reprogrammed to recognize an antigenic marker (e.g., CD19) on a cancer cell and mount an attack on that cell.

When the body recognizes tumor cells as foreign, a natural immune response arises to attack them. Unfortunately, tumors have ways to evade immune surveillance systems and antitumor responses are often too weak to defeat the disease. Rather than relying on the body’s natural response, scientists can now manipulate a patient’s own immune cells so that they latch on to tumor cells by recognizing specific proteins on their surface. A type of immune cell that has been explored for this purpose is the killer (cytotoxic) T cell, which eliminates cells infected by viruses, damaged cells, and tumor cells.

While immunotherapy has been increasingly tested in clinical trials to treat cancer over the past decade, lasting responses have been rare. But an ongoing clinical trial being conducted by James Kochenderfer, M.D., and other CCR researchers shows very promising results in a single patient with recurrent follicular lymphoma. The early results of the trial have been published online in the journal Blood. The research team genetically reprogrammed the patient’s own T cells by inserting a gene designed in the laboratory. The gene encodes for a so-called chimeric antigen receptor (CAR), a protein with a two-pronged function—it enables the cells to recognize tumor cells and activates killer T cells.

When the patient’s disease returned after enduring years of various chemotherapy regimens, he was evaluated and qualified for this experimental treatment involving genetically engineered T cells. His type of lymphoma was characterized by an abnormally high number of malignant B cells. To eliminate malignant B cells, the patient’s own T cells were collected from his blood and genetically modified in the laboratory so they specifically recognize a marker called CD19, which is present on malignant as well as normal B cells. The patient received two infusions of anti-CD19 T cells, followed by eight doses of IL-2, a drug that supports T-cell growth and survival.

No significant adverse reactions occurred as a result of T-cell infusion and the patient experienced impressive partial remission of the lymphoma that lasted 32 weeks. At that time, malignant cells reappeared in two lymph nodes. Notably, B cells were absent in the patient’s blood from 9 weeks until at least 39 weeks after the infusion of engineered T cells, whereas all other types of cells recovered by 9 weeks after treatment. These results demonstrate that anti-CD19 T cells have the potential for specific and long-term elimination of B cells in vivo and encourage further study of anti-CD19-CAR T cells for treatment of lymphoma.

Reference
Blood. 2010 Jul 14. [Epub ahead of print]. Pubmed Link

Reviewed by Donna Kerrigan