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Complementary antitumor immunity induced by plasmid DNA encoding secreted and cytoplasmic human ErbB-2
M P Piechocki1, S A Pilon, W Z Wei
1Karmanos Cancer Institute, Departments of Otolaryngology, and Immunology and Microbiology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|September 7, 2001
Summary
Secreted ErbB-2 (secE2) DNA vaccination protected mice against ErbB-2-positive tumors, comparable to full-length ErbB-2 DNA. Combining secE2 with cytoplasmic ErbB-2 (cytE2) DNA enhanced CTL activity and provided superior tumor protection.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Human ErbB-2 (HER-2/neu) is a validated target in breast cancer therapy.
- DNA vaccination strategies are explored for cancer immunotherapy.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of a DNA vaccine encoding a secreted form of ErbB-2 (secE2).
- To compare the immune response and tumor protection elicited by secE2 DNA versus full-length ErbB-2 DNA.
- To investigate the potential of combining secE2 with cytoplasmic ErbB-2 (cytE2) DNA for enhanced anti-tumor immunity.
Main Methods:
- Construction of a plasmid encoding the N-terminal 505 amino acids of human ErbB-2 (secE2).
- Detection of recombinant secE2 protein secretion.
- Vaccination of BALB/c mice with secE2 DNA, wild-type ErbB-2 DNA, or a combination of secE2 and cytE2 DNA.
- Assessment of ErbB-2-specific antibody (Ab) isotypes (IgG1, IgG2a) and cytotoxic T lymphocyte (CTL) activity.
- Evaluation of tumor protection against D2F2/E2 mouse mammary tumor cells.
Main Results:
- secE2 DNA vaccination induced both IgG1 and IgG2a ErbB-2-specific Abs and protected ~90% of mice against D2F2/E2 tumors.
- Efficacy of secE2 vaccine was comparable to wild-type ErbB-2 DNA, which induced only IgG2a Abs and stronger CTL activity.
- Combined vaccination with secE2 and cytE2 DNA significantly increased CTL activity and provided complete protection against tumor growth.
- secE2 induced a Th2-biased immune response with weak CTL, while E2 induced a Th1 response with strong CTL.
Conclusions:
- secE2 DNA vaccination is effective in inducing humoral immunity and conferring tumor protection.
- Co-administration of secE2 and cytE2 DNA enhances CTL responses and provides superior anti-tumor efficacy.
- Targeting antigens to different subcellular compartments via DNA vaccination is a promising strategy for optimizing anti-cancer immune outcomes.