Peptide Vaccine Stimulates Immune Response in Patients With Breast Cancer

This abstract will be presented at an AACR press conference on Monday, April 2 at 7:30 a.m. CT in room CC20 A/B/C of the Hyatt McCormick Conference Center. Reporters who cannot attend in person may participate by calling in with the following information:U.S. & Canada: (888) 647-7462International: (201) 604-0169

Newswise — CHICAGO — Patients with breast cancer assigned to the HER2-based peptide vaccine AE37 had immunologic responses compared with a control group, according to 24-month results presented at the AACR Annual Meeting 2012, held here March 31 - April 4.

“The theory is that once you form that response to the specific peptide, if the body has a recurrence, it will recognize that cancer as a bad thing, a foreign thing,” said Diane F. Hale, M.D., a research resident in general surgery at Brooke Army Medical Center in Fort Sam, Houston, Texas. “The immune markers could lead us to potentially identify those people who may have a recurrence.”

Of the 217 women enrolled in this prospective, randomized, single-blinded phase II trial, all had completed the standard therapy for breast cancer and were disease-free at the start of the trial.

“We wanted the high-risk patients, those who are at the highest risk for recurrence, so we included those patients who were node-positive or who were node-negative but had poor prognostic factors, such as ER/PR negativity,” Hale said.

Researchers assigned 109 patients to AE37 and the immunoadjuvant granulocyte-macrophage colony-stimulating factor (GM-CSF) and assigned 108 patients to GM-CSF alone in six monthly intradermal injections.

They evaluated in vivo delayed-type hypersensitivity reactions by injecting a small, nontherapeutic dose of the vaccine beneath the patient’s skin and looking for a physical reaction of greater than 5 mm. In the vaccine group, 86 percent of patients showed a significant response compared with 27 percent of patients in the control group.

In addition, researchers evaluated in vitro proliferation responses and found that the vaccine group had more responders than the control group. The latter group had more nonresponders, based on stimulation indexes.

“Naturally, the people in the vaccine group had a significant response compared with the control group because they didn’t have that immune stimulation to the HER2 peptide,” Hale said.

Researchers also measured T regulatory cell responses in 107 patients. Within the vaccine group, “there was a larger percentage of patients who had a decrease in their T regulatory cells” from prevaccination baseline, Hale said. Forty-one patients assigned to the peptide vaccine vs. 28 patient controls had a decrease of more than 90 percent.

Monitoring immunologic tests and T regulatory cells throughout the vaccination process may classify patients as responders and nonresponders. “That can also help us in the future to identify who may recur,” Hale said.

# # #

Press registration for the AACR Annual Meeting 2012 is free to qualified journalists and public information officers: http://www.aacr.org/PressRegistration.

Follow the AACR on Twitter: @aacr #aacrFollow the AACR on Facebook: http://www.facebook.com/aacr.org

About the AACRFounded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policy makers about the value of cancer research and related biomedical science in saving lives from cancer.

For more information about the AACR, visit www.AACR.org.

Presenter: Diane F. Hale, M.D.

Abstract Number: LB-218

Title: Immune response assessment in a phase II trial of AE37 HER2 peptide vaccine

Author Block: Diane F. Hale, Timothy J. Vreeland, Raetasha S. Dabney, G Travis Clifton, Alan K. Sears, Sathibalan Ponniah, Sonia Perez, Nathan Shumway, George E. Peoples, Elizabeth Mittendorf. Brooke Army Medical Center, Ft. Sam Houston, TX, Cancer Vaccine Development Lab, U.S. Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, St. Savas Cancer Hospital, Athens, Greece, Athens, Greece, University of Texas MD Anderson Cancer Center, Houston, TX

Introduction: AE37 is the Ii-Key hybrid of the HER2 derived peptide AE36 (776-790). A phase I trial administering AE37 with the immunoadjuvant GMCSF demonstrated the vaccine to be safe and capable of stimulating CD4+helper T cells with HER2 specific anti-tumor activity. Here we present an analysis of our immunologic testing of our prospective, randomized, single-blinded, phase II trial of the AE37+GMCSF vs. GMCSF alone for the prevention of breast cancer recurrence.Methods: After completion of indicated standard therapy; disease-free, node positive or high risk node negative breast cancer patients were randomized to receive either AE37+GMCSF (VG) or GMCSF (CG) in 6 monthly intradermal inoculations. Patients were enrolled with any level of HER2 expression (IHC 1+ 2+ or 3+). Specific immunologic responses to both AE36 and AE37 were evaluated. In vitro responses were measured using [3H]-thymidine incorporation assay and in vivo responses using delayed-type hypersensitivity (DTH) reactions. T regulatory cells (Tregs) were measured throughout vaccination series. Data was analyzed using Pearson chi-squared tests.Results: To date 217 patients have enrolled (VG=109, CG=108). HER2 over-expression was present in 54 (49.5%) VG and 51 (47.2%) CG, p=0.783. VG had 59 (51.4%) ER positive and CG had 58 (53.7%, p=0.985).The in vitro proliferation responses with a stimulation index (SI) ≥2 were classified as high responders VG 36 (33.0%) vs CG 8 (7.4%, p<0.001 ), SI 1.5-2 were classified as low responders VG 19 (17.4%) vs CG 16 (14.8%, p=0.600) or SI <1.5 as non responders VG 54(49.5%) vs CG 84(77.8%, p<0.001).The in vivo DTH reactions measured in 149 (VG n=86, CG n=63) were stratified as responders with ≥5mm (VG 74(86.0%) vs CG 17(27.0%) p<0.0001) or non responders with <5mm (VG 12 (14.0%) vs CG 46(73.0%) p<0.001). Tregs responses were measured in 107 patients (VG n=56, CG=51) and categorized according to percent change from pre-vaccination baseline as an increase >110% (5(8.9%) VG vs 10 (19.6%) CG, p=0.112), no change 90-110% (10 (17.9%) VG vs 13 (25.5%) CG, p=0.337), or decrease <90% (41 (73.2%) VG vs 28 (54.9%), p=0.048).Conclusion: VG patients had significant immunologic responses compared to CG. VG had a statistical decrease in Tregs compared to CG. Monitoring immunologic tests and Tregs throughout the vaccination process may stratify patients into responders and non responders and thus assist in identifying patients that will have recurrence.