JCI table of contents: March 20, 2008

AUTHOR CONTACT:
Hans-Peter Kiem
Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Phone: (206) 667-4425; Fax: (206) 667-6124; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34371

ACCOMPANYING COMMENTARY

TITLE: HOXB4 and retroviral vectors: adding fuel to the fire

AUTHOR CONTACT:
Cynthia E. Dunbar
National Institutes of Health, Bethesda, Maryland, USA.
Phone: (301) 496-1434; Fax: (301) 496-8396; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=35326

ONCOLOGY: Antitumor immune cells seen taking it slow

In human clinical trials and mouse models of cancer, the transfer of large numbers of immune cells known as CTLs into patients with cancer and mice, respectively, can cause tumor destruction. However, the mechanisms by which CTLs eliminate tumors in this setting remain largely unknown. But now, Philippe Bousso and colleagues, at the Institut Pasteur, France, have provided insight into these mechanism by visualizing tumor cell destruction in real-time in a mouse model of solid tumors.

In the study, transferred CTLs were seen to directly kill tumor cells, with only minimal effects on nontumor cells in the surrounding environment. As an individual CTL was shown to take, on average, 6 hours to destroy a single tumor cell, the authors suggest that directly observing the dynamics of the interaction between tumor cells and CTLs has enabled them to determine one of the factors limiting the efficiency of antitumor CTL responses — time.

TITLE: Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice

AUTHOR CONTACT:
Philippe Bousso
Institut Pasteur, Paris, France.
Phone: 33-1-45688551; Fax: 33-1-45688435; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34388

IMMUNOLOGY: Man versus rat: same type of drug, different response

A phase I clinical trial to test the drug TGN1412 ended only hours after it began in March 2006, when the six healthy volunteers who were administered the drug developed severe clinical symptoms that led to multiple organ failure. The devastating consequences of the drug in humans had not been predicted by studies in animals, in which similar drugs had shown tremendous efficacy in rodent models of autoimmune diseases. New data generated by Holger M. Reichardt and colleagues at the University of Goettingen Medical School, Germany, has now provided more insight into the effects of drugs similar to TGN1412 in rats, but as with the preclinical trials no evidence of the devastating consequences in humans were observed. As pointed out in an accompanying commentary by William St. Clair, at Duke University Medical Center, Durham, these data serve to highlight the different responses of rodents and humans to drugs like TGN1412, and raise “questions about how best to design preclinical studies that can better predict the risks of novel immunotherapeutics in humans.?