HER2 peptide-specific CD8(+) T cells are proportionally detectable long after multiple DNA vaccinations

Area of Science:

• Immunology
• Oncology
• Vaccine Development

Background:

• The human epidermal growth factor receptor 2 (HER2) is a validated target in cancer therapy.
• Developing effective DNA vaccines against HER2 requires strategies to elicit potent cellular and humoral immune responses.

Purpose of the Study:

• To assess the immunogenicity and anti-tumor efficacy of a DNA vaccine encoding HER2-derived cytotoxic T lymphocyte (CTL) and helper epitopes.
• To evaluate the ability of the vaccine to induce HER2-specific CD8(+) T cell responses and antibodies.

Main Methods:

• Construction of a plasmid (pCAGGS147HER2) encoding 147 amino acids of HER2, including CTL (HER2p63) and helper (HER2p1) epitopes.
• Intramuscular immunization in mice followed by assessment of T cell responses using Tetramer, CTL, and ELISPOT assays.
• Quantification of HER2-specific antibodies and evaluation of anti-tumor activity against HER2-positive tumor cells.

Main Results:

• The quantitative ELISPOT assay demonstrated high specificity and sensitivity for detecting functional HER2p63-specific CD8(+) T cells.
• Sustained CD8(+) T cell responses were observed for over 10 months post-immunization, with particularly high numbers after multiple doses.
• HER2 protein-specific IgG antibodies, predominantly IgG2a, were detected for at least 6 months.
• Complete suppression of subcutaneous tumor growth and significant reduction in pulmonary metastases were observed following vaccination.

Conclusions:

• The pCAGGS147HER2 DNA vaccine effectively induces durable HER2-specific CD8(+) T cell immunity and antibody responses.
• This vaccination strategy shows significant potential for controlling HER2-expressing tumors, warranting further investigation for cancer immunotherapy.