GP2 peptide vaccine Phase II
 

HER-2/neu peptide vaccine appears safe for breast cancer survivors
David Douglas


Last Updated: 2009-12-11 16:17:24 -0400 (Reuters Health)

NEW YORK (Reuters Health) - A novel HER-2/neu peptide (GP2) breast cancer vaccine safely elicits a specific immune response in women who are cancer-free after standard treatment for node-negative HER-2/neu-positive tumors.

"HER2/neu is a protein that is highly expressed in breast cancers and many other malignancies," senior investigator Dr. George E. Peoples told Reuters Health. Peptides from this protein, specifically GP2, "are the point of recognition between cytotoxic T cells and HER2/neu-expressing cancer cells."

The GP2 peptide, he added, "can be used to stimulate the immune system to generate many cancer-killing T cells in a very safe manner."

In a November 18th on-line publication in Cancer, Dr. Peoples of Brooke Army Medical Center, Fort Sam Houston, Texas and colleagues report the first phase I study of the vaccine, the goal of which was to identify the optimal doses of GP2 peptide and adjuvant granulocyte-macrophage-colony stimulating factor (GM-CSF). Eighteen disease-free node-negative breast cancer survivors with all levels of HER-2/neu expression were enrolled.

The first three groups, each containing three women, received 6 monthly doses of 100 mcg, 500 mcg and 1000 mcg of GP2, respectively, with 250 mcg of GM-CSF. Eight patients required a GM-CSF dose reduction because of local reactions. The last nine patients each received 500 mcg of GP2 with 125 mcg of GM-CSF.

Ex vivo, GP2-specific CD8+ T cells rose from a baseline median of 0.4% to a median post-vaccination maximum of 1.1%. The response was greatest among those without pre-existing immunity.

In vivo, delayed type hypersensitivity reaction responses rose from a baseline median of 0 to a median of 27.5 mm. Greater responses were seen in patients without pre-existing immunity and also with the 250 mcg GM-CSF dose. There was also an increase in E75-specific CD8+ T cells.

"We have vaccinated breast cancer patients who have been treated with surgery, chemotherapy, and radiation and, therefore, are disease-free but who are at a high risk for recurrence," continued Dr. Peoples.

"This trial has shown the GP2 vaccine to be safe and capable of raising immunity against HER2/neu, but the real question is whether this immunity will result in a clinical benefit and prevent recurrences in these women."

"To answer this crucial question, a randomized phase II clinical trial has been initiated," he said.

Cancer 2010.