Revealing lymphoma growth and the efficacy of immune cell therapies using in vivo bioluminescence imaging

• Published in: Blood Vol. 101; no. 2; pp. 640 - 648
• Main Authors: Edinger, Matthias, Cao, Yu-An, Verneris, Michael R., Bachmann, Michael H., Contag, Christopher H., Negrin, Robert S.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.01.2003; The Americain Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antineoplastic Agents - pharmacology; Applied cell therapy and gene therapy; Biological and medical sciences; Cell Division - drug effects; Cell Division - genetics; Cell Division - radiation effects; Diagnostic Imaging - methods; Female; Genes, Reporter; Hematologic and hematopoietic diseases; Immunotherapy, Adoptive - methods; Killer Cells, Lymphokine-Activated - metabolism; Killer Cells, Lymphokine-Activated - transplantation; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Luminescent Measurements; Lymphoma - diagnosis; Lymphoma - pathology; Lymphoma - therapy; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis - diagnosis; Neoplasm Metastasis - pathology; Radiotherapy; Transduction, Genetic; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; In vivo; Bioluminescence; Treatment; Growth; Lymphoproliferative syndrome; Dissemination; Immunotherapy; Exploration; Medical imagery; Malignant hemopathy; Lymphoma
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-06-1751

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.