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CD40L-Expressing Dendritic Cells Eliminate Breast Tumors in Mice

CD40L-Expressing Dendritic Cells Eliminate Breast Tumors in Mice

ORLANDO—Intratumoral injection of dendritic cells genetically modified to
express CD40 ligand (CD40L) eradicated breast tumors in mice, Zoya R.
Yurkovetsky, a PhD student from the Department of Molecular Genetics and
Biochemistry, University of Pittsburgh School of Medicine, reported at the Era
of Hope Department of Defense Breast Cancer Research Program meeting.

Naïve T cells require help from antigen-presenting cells, the most powerful
being the dendritic cells, Ms. Yurkovetsky said. Dendritic cells are generated
in the bone marrow and travel through the bloodstream to different tissue,
including tumors. Dendritic cells are controlled by different cytokines.

The researchers focused on the CD40 receptor and the protein CD40L, which
plays an active role in dendritic cell generation, migration, functioning,
survival, and critical regulation in the lymph node. Tumors depress CD40L

The researchers injected dendritic cells engineered to express CD40L
(DC/CD40L) directly into TS/A breast tumors in six mice. Control mice were
given saline injections. "We saw a complete rejection of tumor growth in five
out of six mice given DC/CD40L, and in the sixth, the tumor was reduced to a
small size," Ms. Yurkovetsky said. The tumor steadily progressed in the control
animals. "CD40 ligand increased the cytotoxic effect of T cells," she said.

When the researchers rechallenged the treatment group with the same TS/A
tumor, the tumor cells did not proliferate, an indication of immune memory.
"This effect, with generation of specific immune memory, protects the animal
from tumor growth," she said.

The team found that CD40L caused the dendritic cells to produce additional
interleukin-12, an immunostimulatory cytokine previously associated with
antitumor activity.

The researchers also noted that more dendritic cells infiltrated the tumors
in the treatment group than in the control group. "A high concentration of
dendritic cells at the tumor is associated with better prognosis and decreased
metastasis," Ms. Yurkovetsky said.


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