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Evaluation of CD8+ T Cell Activation and Infiltration Into Primary Breast Tumors Following Administration of a Peptide Vaccine

18 Years
Open (Enrolling)
Breast Neoplasms

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Trial Information

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
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.

Inclusion Criteria:

1. Patients with a mass approximately ≥1 cm by breast imaging, BIRADS 5

2. Patients who have been diagnosed, by cytologic or histologic examination, with
adenocarcinoma (including invasive lobular carcinoma) of the breast and have not yet
undergone primary surgery for their disease.

3. All participants must have:

- ECOG performance status of 0 or 1

- Ability and willingness to give informed consent

4. Laboratory parameters as follows:

- HLA-A1, -A2, -A3, or -A31 (+)

- ANC > 1000/mm3

- Platelets > 100,000/mm3

- Hgb > 11 g/dL

- HGBA1C < 7%

- AST and ALT ≤ 2.5 x upper limits of normal (ULN)

- Bilirubin ≤ 2.5 x ULN

- Alkaline phosphatase ≤ 2.5 x ULN

- Creatinine ≤ 1.5 x ULN

- HIV negative

- Hepatitis negative

5. Age ≥ 18 years at the time of registration

6. Participants must have an intact (undissected), nodal basin in the upper extremity
opposite the site of tumor.

Exclusion Criteria:

1. Patients who require neoadjuvant chemotherapy prior to surgery for the treatment of
their disease.

2. Participants with known or suspected allergies to any component of the vaccine.

3. Participants who have an active infection requiring antibiotics.

4. Participants receiving the following medications or treatments at study registration
or within the preceding 30 days are excluded:

- Surgery

- Chemotherapy

- Radiation therapy

- Allergy desensitization injections

- Systemic corticosteroids, administered parenterally or orally. Inhaled
steroids (e.g. Advair®, Flovent®, Azmacort®) are not permitted. Topical
corticosteroids are acceptable, including steroids with very low solubility
administered nasally for local effects only (e.g. Nasonex®).

- Growth factors (e.g., Procrit®, Aranesp®, Neulasta®)

- Any investigational medication

5. Participants may not have been vaccinated previously with any of the synthetic
peptides included in this protocol.

6. Pregnancy during vaccine administration. Female participants of childbearing
potential must have a negative pregnancy test (urinary or serum β-HCG) prior to
administration of the first vaccine dose. Males and females must agree, in the
consent form, to use effective birth control methods during the course of

7. Female participants must not be breastfeeding.

8. Participants in whom there is a medical contraindication or potential problem in
complying with the requirements of the protocol, in the opinion of the investigator.

9. Participants classified according to the New York Heart Association classification as
having Class III or IV heart disease.

10. Participants must not have had prior autoimmune disorders requiring cytotoxic or
immunosuppressive therapy, or autoimmune disorders with visceral involvement.
Participants with an active autoimmune disorder requiring these therapies are also
excluded. The following will not be exclusionary:

- The presence of laboratory evidence of autoimmune disease (e.g. positive ANA
titer) without symptoms

- Clinical evidence of vitiligo

- Other forms of depigmenting illness

- Mild arthritis requiring NSAID medications

11. Body weight < 110 lbs (without clothes)

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To evaluate whether a multi-peptide vaccine induces T cells that traffic to and penetrate into human primary breast cancers.

Outcome Time Frame:

22 days following initiation of the vaccines

Safety Issue:


Principal Investigator

David R. Brenin, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Virginia


United States: Food and Drug Administration

Study ID:




Start Date:

May 2009

Completion Date:

May 2013

Related Keywords:

  • Breast Neoplasms
  • breast cancer
  • peptide vaccine
  • immunotherapy
  • Breast Neoplasms
  • Neoplasms



University of Virginia Health SystemCharlottesville, Virginia  22903