Originally published as JCO Early Release 10.1200/JCO.2009.22.3883 on September 14 2009

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Phase I Active Immunotherapy With Combination of Two Chimeric, Human Epidermal Growth Factor Receptor 2, B-Cell Epitopes Fused to a Promiscuous T-Cell Epitope in Patients With Metastatic and/or Recurrent Solid Tumors

From the Department of Obstetrics and Gynecology, Division of Reproductive Biology and Vaccine Research; and Division of Gynecology Oncology; Department of Internal Medicine, Division of Hematology/Oncology; and Division of Surgery; and Department of Microbiology, Comprehensive Cancer Center and Solove Research Institute, Ohio State University, Columbus, OH.

Corresponding author: Pravin T.P. Kaumaya, PhD, Tzagournis Medical Research, Ste 316, 420 W 12th Ave, Columbus, OH 43210; e-mail: kaumaya.1{at}osu.edu.

Purpose To evaluate the maximum-tolerated dose (MTD), safety profile, and immunogenicity of two chimeric, B-cell epitopes derived from the human epidermal growth factor receptor (HER2) extracellular domain in a combination vaccine with a promiscuous T-cell epitope (ie, MVF) and nor-muramyl-dipeptide as adjuvant emulsified in SEPPIC ISA 720.

Patients and Methods Eligible patients with metastatic and/or recurrent solid tumors received three inoculations on days 1, 22, and 43 at doses of total peptide that ranged from 0.5 to 3.0 mg. Immunogenicity was evaluated by enzyme-linked immunosorbent assay, flow cytometry, and HER2 signaling assays.

Results Twenty-four patients received three inoculations at the intended dose levels, which elicited antibodies able to recognize native HER2 receptor and inhibited both the proliferation of HER2-expressing cell lines and phosphorylation of the HER2 protein. The MTD was determined to be the highest dose level of 3.0 mg of the combination vaccine. There was a significant increase from dose level 1 (0.5 mg) to dose level 4 (3.0 mg) in HER2-specific antibodies. Four patients (one each with adrenal, colon, ovarian, and squamous cell carcinoma of unknown primary) were judged to have stable disease; two patients (one each with endometrial and ovarian cancer) had partial responses; and 11 patients had progressive disease. Patients with stable disease received 6-month boosts, and one patient received a 20-month boost.

Conclusion The combination vaccines were safe and effective in eliciting antibody responses in a subset of patients (62.5%) and were associated with no serious adverse events, autoimmune disease, or cardiotoxicity. There was preliminary evidence of clinical activity in several patients.

Supported in part by National Institutes of Health National Cancer Institute Grant No. CA094555 (P.T.P.K.).

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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