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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)5270-5277
Number of pages8
JournalJournal of Clinical Oncology
Volume27
Issue number31
DOIs
StatePublished - Nov 1 2009
Externally publishedYes

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B-Lymphocyte Epitopes
Active Immunotherapy
T-Lymphocyte Epitopes
Neoplasms
Combined Vaccines
Maximum Tolerated Dose
human ERBB2 protein
Acetylmuramyl-Alanyl-Isoglutamine
Antibodies
Endometrial Neoplasms
Epidermal Growth Factor Receptor
Ovarian Neoplasms
Autoimmune Diseases
Antibody Formation
Squamous Cell Carcinoma
Flow Cytometry
Colon
Enzyme-Linked Immunosorbent Assay
Phosphorylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

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

In: Journal of Clinical Oncology, Vol. 27, No. 31, 01.11.2009, p. 5270-5277.

Research output: Contribution to journalArticle

Kaumaya, PTP, Foy, KC, Garrett, J, Rawale, SV, Vicari, D, Thurmond, JM, Lamb, T, Mani, A, Kane, Y, Balint, CR, Chalupa, D, Otterson, GA, Shapiro, CL, Fowler, JM, Grever, MR, Bekaii-Saab, TS & Carson, WE 2009, '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', Journal of Clinical Oncology, vol. 27, no. 31, pp. 5270-5277. https://doi.org/10.1200/JCO.2009.22.3883
Kaumaya, Pravin T P ; Foy, Kevin Chu ; Garrett, Joan ; Rawale, Sharad V. ; Vicari, Daniele ; Thurmond, Jennifer M. ; Lamb, Tammy ; Mani, Aruna ; Kane, Yahaira ; Balint, Catherine R. ; Chalupa, Donald ; Otterson, Gregory A. ; Shapiro, Charles L. ; Fowler, Jeffrey M. ; Grever, Michael R. ; Bekaii-Saab, Tanios S. ; Carson, William E. / 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. In: Journal of Clinical Oncology. 2009 ; Vol. 27, No. 31. pp. 5270-5277.
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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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T1 - 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

AU - Kaumaya, Pravin T P

AU - Foy, Kevin Chu

AU - Garrett, Joan

AU - Rawale, Sharad V.

AU - Vicari, Daniele

AU - Thurmond, Jennifer M.

AU - Lamb, Tammy

AU - Mani, Aruna

AU - Kane, Yahaira

AU - Balint, Catherine R.

AU - Chalupa, Donald

AU - Otterson, Gregory A.

AU - Shapiro, Charles L.

AU - Fowler, Jeffrey M.

AU - Grever, Michael R.

AU - Bekaii-Saab, Tanios S.

AU - Carson, William E.

PY - 2009/11/1

Y1 - 2009/11/1

N2 - 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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