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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-06-1751.
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Blood, 15 January 2003, Vol. 101, No. 2, pp. 640-648
NEOPLASIA
Revealing lymphoma growth and the efficacy of immune cell
therapies using in vivo bioluminescence imaging
Matthias Edinger,
Yu-An Cao,
Michael R. Verneris,
Michael H. Bachmann,
Christopher H. Contag, and
Robert S. Negrin
From the Division of Bone Marrow Transplantation,
Department of Medicine; and Department of Pediatrics; Stanford
University School of Medicine; Stanford, CA.
Cancer therapeutics have achieved success in the treatment of a
variety of malignancies, however, relapse of disease from small numbers
of persistent tumor cells remains a major obstacle. Advancement of
treatment regimens that effectively control minimal residual disease
and prevent relapse would be greatly accelerated if sensitive and
noninvasive assays were used to quantitatively assess tumor burden in
animal models of minimal residual disease that are predictive of the
human response. In vivo bioluminescence imaging (BLI) is an assay for
the detection of small numbers of cells noninvasively and enables the
quantification of tumor growth within internal organs. Fusion genes
that encode bioluminescent and fluorescent reporter proteins
effectively couple the powerful in vivo capabilities of BLI with the
subset-discriminating capabilities of fluorescence-activated cell
sorting. We labeled 2 murine lymphoma cell lines with dual
function reporter genes and monitored radiation and chemotherapy as
well as immune-based strategies that employ the tumorcidal activity of
ex vivo-expanded CD8+ natural killer (NK)-T
cells. Using BLI we were able to visualize the entire course of
malignant disease including engraftment, expansion, metastasis,
response to therapy, and unique patterns of relapse. We also labeled
the effector NK-T cells and monitored their homing to the sites of
tumor growth followed by tumor eradication. These studies reveal the
efficacy of immune cell therapies and the tempo of NK-T cell
trafficking in vivo. The complex cellular processes in bone marrow
transplantation and antitumor immunotherapy, previously inaccessible to
investigation, can now be revealed in real time in living animals.
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