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HER2-specific T-cell immune responses in patients vaccinated with truncated HER2 protein complexed with nanogels of cholesteryl pullulan.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2006 Dec 15; Vol. 12 (24), pp. 7397-405. - Publication Year :
- 2006
-
Abstract
- Purpose: We developed a complex of tumor antigen protein with a novel nanoparticle antigen delivery system of cholesteryl pullulan (CHP). To target HER2 antigen, we prepared truncated HER2 protein 1-146 (146HER2) complexed with CHP, the CHP-HER2 vaccine. We designed a clinical study to assess the safety of the vaccine and HER2-specific T-cell immune responses measured by the newly developed enzyme-linked immunospot assay with mRNA-transduced phytohemagglutinin-stimulated CD4(+) T cells in HLA-A2402-positive patients with therapy-refractory HER2-expressing cancers.<br />Experimental Design: Nine patients with various types of solid tumors were enrolled. Each patient was s.c. vaccinated biweekly with 300 microg of CHP-HER2 vaccine for three times followed by booster doses. HER2-specific T-cell responses were evaluated by enzyme-linked immunospot assay by targeting autologous phytohemagglutinin-stimulated CD4(+) T cells transduced with 146HER2-encoding mRNA to cover both identified peptides and unknown epitopes for MHC class I and class II that might exist in the sequence of the vaccine protein.<br />Results: CHP-HER2 vaccine was well tolerated; the only adverse effect was grade 1 transient skin reaction at the sites of vaccination. HER2-specific CD8(+) and/or CD4(+) T-cell immune responses were detected in five patients who received four to eight vaccinations, among whom both T-cell responses were detected in these patients. In four patients with CD8(+) T-cell responses, two patients reacted to previously identified HER2(63-71) peptide and the other two reacted only to 146HER2 mRNA-transduced cells.<br />Conclusions: CHP-HER2 vaccine was safe and induced HER2-specific CD8(+) and/or CD4(+) T-cell immune responses.
- Subjects :
- Adult
Aged
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Female
Glucans therapeutic use
Humans
Immunization, Passive methods
Male
Middle Aged
Nanogels
Neoplasms metabolism
Polyethylene Glycols therapeutic use
Polyethyleneimine therapeutic use
Protein Structure, Tertiary
Receptor, ErbB-2 metabolism
Recombinant Fusion Proteins therapeutic use
T-Lymphocytes, Cytotoxic immunology
Cancer Vaccines chemistry
Cancer Vaccines therapeutic use
Glucans chemistry
Neoplasms therapy
Receptor, ErbB-2 chemistry
Receptor, ErbB-2 immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 12
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 17189412
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-06-1546