JCI table of contents: Feb. 21, 2008

It is possible to cure some individuals with leukemia by infusing them with immune cells known as lymphocytes during a surgical procedure known as hematopoietic stem cell transplantation (HCT). However, little is known about effective HCT approaches to treating individuals with solid tumors. In a new study, Richard Childs and colleagues, at the National Institutes of Health, Bethesda, have outlined an HCT approach for the treatment of metastatic kidney cancer that caused tumor regression associated with a tumor-targeted lymphocyte response in several patients.

The authors detected tumor-targeted lymphocytes known as CD8+ T cells in the blood of patients with metastatic kidney cancer who had received nonmyeloablative HCT. Further analysis identified the tumor peptide recognized by these CD8+ T cells and it was found to be a fragment of a protein not expressed by healthy cells. The gene responsible for making this protein was part of a region of human chromosome 6 derived from a human endogenous retrovirus (HERV) type E. The authors therefore suggested that HERV-E is activated in metastatic kidney cancer providing a protein target for the immune system. This information might be useful when considering the development of immunotherapeutic approaches to treating individuals with this form of cancer.

TITLE: Regression of human kidney cancer following allogeneic stem cell transplantation is associated with recognition of an HERV-E antigen by T cells

AUTHOR CONTACT:
Richard W. Childs,
National Institutes of Health, Bethesda, Maryland, USA.
Phone: (301) 451-7128; Fax: (301) 480-2664; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34409

HEMATOLOGY: New protein seen to have a role in blood clot formation

New data generated by Bruce Furie and colleagues at the Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, have identified a role for protein disulfide isomerase (PDI) in blood clot formation (also known as thrombus formation) in mice.

Using in vivo imaging techniques it was observed that the expression of PDI increased in a thrombus that was forming following blood vessel damage. Furthermore, inhibition of PDI using either an agent known as bacitracin or an antibody specific for PDI inhibited thrombus formation. More detailed analysis indicated that PDI was also important for the generation of fibrin following damage to the wall of a blood vessel, a key step in thrombus formation. However, further studies are required to determine whether inhibiting PDI might provide a new approach to treating human conditions associated with aberrant blood clot formation, such as several forms of heart diseases and strokes, or whether the risks of such an approach would outweigh the benefits.

TITLE: A critical role for extracellular protein disulfide isomerase during thrombus formation in mice

AUTHOR CONTACT:
Bruce Furie
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617) 754-1200; Fax: (617) 754-1234; E-mail: .

View the PDF of this article at: https://www.the-jci.org/article.php?id=34134