Vaccine strategies are being designed to battle cancer, but their use for metastatic melanoma is a challenge. Effective vaccines against established tumors require tumor-reactive T cells to traffic to the sites of the tumors and are locally activated there in order to kill cancer cells. A problem is that the T cells lose their tumor-killing power once they reach the environment surrounding the tumor. This happens because T cells decrease stimulatory molecules including one called B7.1.
In a study appearing online on June 2 in advance of the print publication of the July 1 print issue of the Journal of Clinical Investigation, Howard Kaufman and colleagues from Columbia University manipulate the local tumor environment as a method for improving systemic anti-tumor immunity. This concept has been suggested in mouse models but had not established in the clinical setting. The data represent the first clinical trial to directly inject a vaccinia virus expressing the B7.1 costimulatory molecule into humans with melanoma.
The researchers show that this vaccine is safe and feasible to use for local delivery into established melanoma lesions. 2 of the injected lesions showed a partial response and 3 were stable. One patient remained alive without disease recurrence for 59 months after vaccination without any other therapy. This approach may be useful for altering the tumor environment in order to induce anti-tumor immunity and provides a foundation upon which other vaccine strategies can be contemplated for local delivery.
TITLE: Targeting the local tumor microenvironment by vaccinia virus expressing B7.1 for the treatment of melanoma
AUTHOR CONTACT:
Howard Kaufman
Columbia University, New York, NY USA
Phone: 212-342-6042; Fax: 212-342-0234; E-mail: hlk2003@columbia.edu
View the PDF of this article at:https://www.the-jci.org/article.php?id=24624
Journal
Journal of Clinical Investigation