News
USMCI and USUHS Molecular & Cell Biology Seminar
When: Wednesday, March 18, 2009 - 3:30pm
Where: Lecture Room A - USUHS
Presented by:
Jeffrey Rosen, PhD
C.C. Bell Professor of Molecular and Cellular Biology and Medicine
Distinguished Service Professor
Baylor College of Medicine
Houston, TX
The Seminar is presented by the USUHS MCB Graduate Program & co-sponsored by the US Military Cancer Institute.
USUHS: 4301 Jones Bridge Road, Bethesda, Maryland 20814
USMCI and USUHS Molecular & Cell Biology Seminar
“Novel Signaling in Cancer Cells and Development of Targeted Therapy”
When: Wednesday, February 18, 2009 - 3:30pm
Where: Lecture Room A - USUHS
Presented by:
Mien-Chie Hung, PhD
Professor & Chair, Molecular & Cellular Oncology
Professor, Surgical Oncology
Director, Breast Cancer Basic Research Program
University of Texas M.D. Anderson Cancer Center
Houston, TX
USMCI congratulates the newly appointed Attending Physician to Congress
Secretary of Defense Robert M. Gates announced today that the President has nominated Navy Capt Brian P. Monahan, a former Associate Director of the USMCI, for appointment to the grade of rear admiral and assignment as attending physician to Congress. Monahan is currently serving as deputy attending physician to Congress.
USMCI Clinical Trials Program published makes cover of the journal Cancer
Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to
prevent breast cancer recurrence
BACKGROUND.
E75, a HER-2/neu-derived peptide, was administered as a preventive
vaccine with granulocyte-macrophage-colony-stimulating factor (GM-CSF)
in disease-free lymph node-positive (NP) and lymph node-negative (NN)
breast cancer (BCa) patients. The optimal biologic dose (OBD) was
determined based on toxicity and immunologic response.
METHODS.
Patients were vaccinated over 6 months (3, 4, or 6 times) with
different doses of E75 plus GM-CSF. Toxicities were graded per National
Cancer Institute Common Terminology Criteria. GM-CSF was reduced for
significant toxicity. Immunologic response was measured by delayed type
hypersensitivity test (DTH), and E75-specific CD8+ T-cells were
quantified with human leukocyte antigen-A2:immunoglobulin G dimer and
flow cytometry.
RESULTS.
Ninety-nine patients (48 NP and 51 NN) were vaccinated in 7 dose
groups. The OBD was 1000 g E75 plus 250 g GM-CSF monthly × 6. The
optimal dose group (ODG, n = 29) experienced similar toxicities to the
suboptimal dose group (SDG, n = 70), which was comprised of the
remaining 6 groups. The ODG demonstrated a trend toward an increase in
the average postvaccine dimer (0.87 ± 0.10% vs 0.67 ± 0.05%; P = .07),
a significantly larger DTH response (21.5 ± 2.5 mm vs 11.3 ± 1.3 mm; P
= .0002), and a trend toward decreased recurrences (3.4% vs 12.9%; P =
.27). Compared with the SDG, the ODG had larger tumors (percentage T2:
55% vs 23%; P = .004), more positive lymph nodes (percentage NP: 76% vs
37%; P = .001), and higher grade tumors (percentage grade 3: 52% vs
30%; P = .07), but a shorter median follow-up time (20 months vs 32
months; P < .001).
CONCLUSIONS.
Compared with suboptimally dosed patients, the optimally dosed E75
vaccine in disease-free BCa patients had similar toxicity but enhanced
HER-2/neu-specific immunity that may lead to decreased recurrences with
additional follow-up. Cancer 2008;113:1666-75.
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USMCI Clinial Trials Program paper is published in the journal of Clinical Cancer Research
Purpose: E75 is an immunogenic peptide fromthe HER2/neu protein, which
is overexpressed in
many breast cancer patients.We have conducted two overlapping E75
vaccine trials to prevent
recurrence in node-positive (NP) and node-negative (NN) breast cancer
patients.
Experimental Design: E75 (HER2/neu 369-377) + granulocytemacrophage
colony-stimulating
factor was given intradermally to previously treated, disease-free NP
breast cancer patients in a
dose escalation safety trial and to NN breast cancer patients in a dose
optimization study. Local
and systemic toxicity was monitored. Immunologic responses were
assessed using in vitro assays
and in vivo delayed-type hypersensitivity responses. Clinical
recurrences were documented.
Results: One hundred and eighty-six patients were enrolled in the two
studies (NP, 95; NN, 91).
Humanleucocyte antigen A 2 (HLA-A 2) and HLA-A 3 patients were
vaccinated (n =101),whereas
all others (n = 85) were followed prospectively as controls. Toxicities
were minimal, and a
dose-dependent immunologic response to the vaccine was shown. Planned
primary analysis
revealed a recurrence rate of 5.6% in vaccinated patients compared with
14.2% in the controls
(P = 0.04) at a median of 20 months follow-up. As vaccine-specific
immunity waned over
time, the difference in recurrence lost significance at 26 months
median follow-up (8.3% versus
14.8%); however, a significant difference in the pattern of recurrence
persisted.
Conclusions: E75 is safe and effective in raising a dose-dependent
HER2/neu immunity in
HLA-A2 and HLA-A3 NP and NN breast cancer patients. More importantly,
E75 may reduce
recurrences in disease-free, conventionally treated, high-risk breast
cancer patients. These
findingswarrant a prospective, randomized phase III trial of the E75
vaccine with periodic booster
to prevent breast cancer recurrences.
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USMCI Conducting Phase II Clinical Trial for Breast Cancer Vaccine
The United States Military Cancer Institute's (USMCI) Clinical Trials Group is engaged in ground-breaking research working towards cancer solutions in both military and civilian populations. One exciting study in which USMCI is currently involved is a prospective, randomized, multi-center Phase, II clinical trial investigating whether a new vaccine can prevent recurrence in disease-free, conventionally treated, node-positive and high-risk node-negative breast cancer patients who are at significant risk for recurrence. > More