Results of the first phase 1 clinical trial of the HER‐2/neu peptide (GP2) vaccine in disease‐free breast cancer patients |
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| Authors: | Mark G. Carmichael MD Linda C. Benavides MD Jarrod P. Holmes MD Jeremy D. Gates MD Elizabeth A. Mittendorf MD Sathibalan Ponniah PhD George E. Peoples MD |
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| Affiliation: | 1. Cancer Vaccine Development Program, United States Military Cancer Institute, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland;2. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Fort Sam Houston, Texas;3. Department of Hematology and Medical Oncology, Naval Medical Center San Diego, San Diego, California;4. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas;5. Department of Surgery, General Surgery Service, Brooke Army Medical Center, Fort Sam Houston, TexasFax: (210) 916‐6658. |
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| Abstract: | BACKGROUND: HER‐2/neu, overexpressed in breast cancer, is a source of immunogenic peptides that include GP2 and E75. Phase 2 testing of E75 as an adjuvant vaccine has suggested a clinical benefit. GP2, derived from the transmembrane portion of HER‐2/neu, has differing binding characteristics and may be more immunogenic than E75. Results of the first phase 1 trial of GP2 peptide vaccine are presented. METHODS: Disease‐free, lymph node‐negative, human leukocyte antigen (HLA)‐A2+ breast cancer patients were enrolled. This dose escalation trial included 4 groups to determine safety and optimal GP2 peptide/granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) dose. Toxicities were monitored. Immunologic response was assessed ex vivo via the HLA‐A2:immunoglobulin dimer assay to detect GP2‐specific CD8+ T cells (and E75‐specific CD8+ T cells to assess epitope spreading) and in vivo via delayed type hypersensitivity (DTH) reaction (medians/ranges). RESULTS: Eighteen patients were enrolled. All toxicities were grade ≤2. Eight (88.9%) of 9 patients in the first 3 dose groups required GM‐CSF dose reductions for local reactions ≥100 mm or grade ≥2 systemic toxicity. GM‐CSF dose was reduced to 125 μg for the final dose group. All patients responded immunologically ex vivo (GP2‐specific CD8+ T cells from prevaccination to maximum, 0.4% [0.0%‐2.0%] to 1.1% [0.4%‐3.6%], P < .001) and in vivo (GP2 pre‐ to postvaccination DTH, 0 mm [0.0‐19.5 mm] to 27.5 mm [0.0‐114.5 mm, P < .001). E75‐specific CD8+ T cells also increased in response to GP2 from prevaccination to maximum (0.8% [0.0%‐2.41%] to 1.6% [0.86%‐3.72%], P < .001). CONCLUSIONS: The GP2 peptide vaccine appears safe and well tolerated with minimal local/systemic toxicity. GP2 elicited HER‐2/neu–specific immune responses, including epitope spreading, in high‐risk, lymph node‐negative breast cancer patients. These findings support further investigation of the GP2 vaccine for the prevention of breast cancer recurrence. Cancer 2010. © 2010 American Cancer Society. |
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| Keywords: | breast cancer GP2 HER‐2/neu peptide vaccine |
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