Visualizing the kinetics of tumor-cell clearance in living animals

Visualizing the kinetics of tumor-cell clearance in living animals

Departments of ^*Medicine and ^‡Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5208

Edited by Irving L. Weissman, Stanford University School of Medicine, Stanford, CA, and approved August 20, 1999 (received for review May 6, 1999)

Abstract

Evaluation of potential antineoplastic therapies would be enhanced by noninvasive detection of tumor cells in living animals. Because light is transmitted through mammalian tissues, it was possible to use bioluminescence to monitor (both externally and quantitatively) growth and regression of labeled human cervical carcinoma (HeLa) cells engrafted into immunodeficient mice. The efficacy of both chemotherapy and immunotherapeutic treatment with ex vivo expanded human T cell-derived effector cells was evaluated. In the absence of therapy, animals showed progressive increases in signal intensity over time. Animals treated with cisplatin had marked reductions in tumor signal; 5′-fluorouracil was less effective, and cyclophosphamide was ineffective. Immunotherapy dramatically reduced signals at high effector-to-target cell ratios, and significant decreases were observed with lower ratios. This model system allowed sensitive, quantitative, real-time spatiotemporal analyses of the dynamics of neoplastic cell growth and facilitated rapid optimization of effective treatment regimens.

Footnotes

↵ † V.M. and A.A.T. contributed equally to this work.
↵ § To whom reprint requests should be addressed. E-mail: ccontag{at}cmgm.stanford.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

SCID,

severe combined immunodeficiency;

CIK,

cytokine-induced killer;

5′-FU,

5′-fluorouracil;

E:T ratio,

effector-to-target cell ratio