ORLANDOBioluminescent 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."