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research
The Klingemann lab is
interested in translational research projects that will make stem cell
transplants for bone marrow cancers safer and more universally available. The
goal of the Stem Cell Transplant Research lab is to engineer a stem cell
graft that provides healthy stem cells along with cytotoxic immune cells
specifically recognizing leukemia/lymphoma.
Natural killer (NK) cells
are genetically engineered to make them home to tumor sites and more selectively
and specifically recognize leukemia and lymphoma cells. The goal is to further
reduce the toxicities of chemotherapy and radiation and put immune cells to
work.
The Klingemann lab
discovered the NK-92 cell line, that is used by research teams worldwide to
study the biology of NK cells. First clinical trials in cancer patients have
been completed with NK-92 cells. Based on studies with NK-92, the lab is now
developing NK cells from human cord blood to become targeted to leukemia and
lymphoma cells by genetically modifying the cells. This is being accomplished by
the introduction of chimeric antigen receptors (CAR), now available against CD19
and CD20 as well as a high affinity Fc receptor. This allows to combine NK
treatment with monoclonal antibodies that use ADCC as their primary mechanism of
tumor kill. In addition to making NK cells better recognize tumor cells, we
also working on improving their homing to malignant cells and augment their
cytotoxicity locally.
The laboratory was the first
to discover that mesechymal
stem cells from the Wharton’s
Jelly of the umbilical cord (UC-MSC) can support faster engraftment of
hematopoietic stem cells after cord blood transplants into immunocompromised
mice. US-MSC are now being explored for expansion of NK cells for
potential applications in human trials.
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