Evaluating the T Cell Response to a Peptide-based Vaccine in Patients With Breast Cancer (Breast 37)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Evaluation of CD8+ T Cell Activation and Infiltration Into Primary Breast Tumors Following Administration of a Peptide Vaccine|
- To evaluate whether a multi-peptide vaccine induces T cells that traffic to and penetrate into human primary breast cancers. [ Time Frame: 22 days following initiation of the vaccines ] [ Designated as safety issue: No ]
- To characterize the T cell response to a peptide-based vaccine in terms of antigen specificity and the induction of differentiated effector cells, both in the peripheral blood and within the tumor microenvironment. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||May 2009|
|Study Completion Date:||February 2012|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
|Experimental: 9 Peptide Vaccine||
Biological: 9 Peptides from Her-2/neu, CEA, & CTA
Each vaccination will be administered on days 1, 8, 15, 36, 43, and 50. All participants will receive 9 class I MHC-restricted synthetic peptides and a class II MHC-restricted tetanus helper peptide administered in Montanide ISA-51. The vaccine will be administered subcutaneously (1 ml) and intradermally (1ml) at a single vaccination site.
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 cancer patients.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00892567
|United States, Virginia|
|University of Virginia Health System|
|Charlottesville, Virginia, United States, 22908|
|Principal Investigator:||David R. Brenin, M.D.||University of Virginia|