Evaluation of CD8+ T Cell Activation and Infiltration Into Primary Breast Tumors Following Administration of a Peptide Vaccine
Just under 200,000 American women will be diagnosed with breast cancer this year. Standard
breast cancer therapies have long included surgical resection, chemotherapy, radiation
therapy, and hormonal therapy. However, other immune therapies are now being explored for
the treatment of breast cancer, including peptide-based vaccines. In support of directed T
cell therapies for breast cancer, antigenic epitopes from breast cancer-associated proteins
such as Her-2/neu and the MAGE gene family have been identified, and vaccines containing
peptides derived from these proteins have been shown to be safe and immunogenic in breast
Results from successful immune therapy approaches, for various human and murine cancers,
have shown that antitumor effects can be mediated by T cells, which is proof-of-principle
that the immune system, and in particular, T cells, can reject tumor. Overall, however, the
complete clinical response rate for T cell mediated immunotherapies has been low. There are
at least two possibilities to explain why this may be the case. First, tumor reactive T
cells may not traffic to tumors. Second, tumor reactive T cells may not have adequate
effector function within the tumor microenvironment. Neither of these hypotheses has been
adequately explored, though there are data suggesting that either or both may represent
obstacles to successful immune therapy. In order to improve upon the clinical response rate
with vaccines, we need to address the questions of whether vaccine-induced T cells traffic
to tumor and exhibit effector function within the tumor.
Specifically for breast cancer, there are opportunities for targeting T cells against
primary tumors with the intent of providing immune protection early in the disease course.
In the proposed clinical trial we will be administering a peptide-based vaccine and
monitoring responses to the vaccine at the site of primary tumor. Peptide vaccines are
unique in that they provide an opportunity to monitor directly the T cell response to
defined antigens, enabling dissection of the immune response pre- and post-vaccination. The
proposed analyses are designed to test the hypotheses that vaccination 1) enhances T cell
infiltration into tumor and 2) induces T cells to become activated and fully differentiate
into effector cells. The goals of this proposal are to define the extent to which these two
processes occur following vaccination and to identify opportunities for improving tumor
targeting and T cell effector function in human breast cancer.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate whether a multi-peptide vaccine induces T cells that traffic to and penetrate into human primary breast cancers.
22 days following initiation of the vaccines
David R. Brenin, M.D.
University of Virginia
United States: Food and Drug Administration
|University of Virginia Health System||Charlottesville, Virginia 22903|