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Bioluminescent Imaging Tracks Responses

Bioluminescent Imaging Tracks Responses

ORLANDO—Bioluminescent imaging may provide a noninvasive method to monitor
the effect of new biologic and immunomodulatory treatments for cancer, Matthias
G. Edinger, MD, said at the 43rd Annual Meeting of the American Society of
Hematology (abstract 1817). Dr. Edinger is in the Division of Bone Marrow
Transplantation at Stanford University School of Medicine.

In this study, bioluminescent imaging of tumor responses and effector cells
showed that adoptive transfer of expanded CD8+ NKT cells can improve long-term
survival and reduce graft-vs-host disease (GVHD) in an animal model of lymphoma
treated with allogeneic bone marrow transplantation (BMT). The new method also
showed that cytotoxic cells trafficked to the tumor site and remained there
until the tumor was eradicated.

Michael A. Caligiuri, MD, who introduced the presentation, said that new
approaches to cancer therapy are taking advantage of T-cell characteristics, specifically "the receptors they use
to see what is going on in the body." Dr. Caligiuri is director for
clinical research at Ohio State University’s Comprehensive Cancer Center,
Columbus.

In allogeneic BMT, the donor T cell "sees" different major
histocompatibility complex (MHC) antigens on the tumor cell surface and
launches a graft-vs-leukemia effect that eliminates some tumors left behind
even by high-dose chemotherapy. The downside is that this also increases the
risk of GVHD.

Natural killer (NK) cells, unlike T cells, "see" the absence of
MHC class I molecules. NKT cells are midway between the two. Dr. Caligiuri said
that they detect MHC components, as T cells do, but also can detect the absence
of MHC, as NK cells do.

The Animal Models

"Since light is transmitted through mammalian tissues at low levels,
cells expressing the bioluminescent reporter gene luciferase (Luc) can be
detected within living mice using low light imaging CCD [charged couple device]
cameras," Dr. Edinger said. Luc uses the substrate luceriferin, a small,
water-soluble molecule that rapidly penetrates cells and tissues after IV or IM
injection. "Using this technique," he said, "we established
animal models of leukemia and lymphoma that allow us to localize and quantify
tumor cells noninvasively in vivo."

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