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

Pravin T.P Kaumaya; Kevin Chu Foy; Joan Garrett; Sharad V Rawale; Daniele Vicari; Jennifer M Thurmond; Tammy Lamb; Aruna Mani; Yahaira Kane; Catherine R Balint; Donald Chalupa; Gregory A Otterson; Charles L Shapiro; Jeffrey M Fowler; Michael R Grever; Tanios S Bekaii-Saab; William E Carson

doi:10.1200/JCO.2009.22.3883

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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

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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

Pravin T.P Kaumaya, Kevin Chu Foy, Joan Garrett, Sharad V Rawale, Daniele Vicari, Jennifer M Thurmond, Tammy Lamb, Aruna Mani, Yahaira Kane, Catherine R Balint, …

Journal of clinical oncology, Vol.27(31), pp.5270-5277

2009-11-01

DOI: https://doi.org/10.1200/JCO.2009.22.3883

PMCID: PMC2773479

PMID: 19752336

Abstract

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.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.119 Breast Cancer Scanning; 1.119.259 HER2
Web Of Science research areas: Oncology
ESI research areas: Clinical Medicine

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Title: 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
Creators: Pravin T.P Kaumaya - 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
Kevin Chu Foy - 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
Joan Garrett - 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
Sharad V Rawale - 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
Daniele Vicari - 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
Jennifer M Thurmond - 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
Tammy Lamb - 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
Aruna Mani - 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
Yahaira Kane - 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
Catherine R Balint - 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
Donald Chalupa - 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
Gregory A Otterson - 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
Charles L Shapiro - 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
Jeffrey M Fowler - 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
Michael R Grever - 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
Tanios S Bekaii-Saab - 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
William E Carson - 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
Publication Details: Journal of clinical oncology, Vol.27(31), pp.5270-5277
Language: English
Resource Type: Journal article
PMID: 19752336
PMCID: PMC2773479
Record Identifier: 991031614433002976