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Peptides derived from a wild-type murine proto-oncogene c-erbB-2/HER2/neu can induce CTL and tumor suppression in
1Second Department of Surgery, Nagasaki University School of Medicine, Japan.
Abstract:
In this analysis, we examined whether peptides derived from a wild-type murine proto-oncogene, c-erbB-2, function as tumor rejection Ags. Expression of murine c-erbB-2 examined by means of reverse transcription-PCR was observed in several normal adult tissues, such as intestine, kidney, and testis. We then transduced human and murine c-erbB-2 cDNA into two mutually noncross-reactive fibrosarcoma lines of BALB/c origin, CMS7 and CMS17. In BALB/c mice immunized with CMS17HE (CMS17 transduced with human c-erbB-2 cDNA), the growth of subsequently challenged CMS7HE (CMS7 transduced with human c-erbB-2 cDNA) was significantly suppressed. CTL against human c-erbB-2-expressing cells were generated from BALB/c spleen cells in vivo and in vitro sensitized by CMS17HE. The CTL activity was also directed against murine c-erbB-2-expressing cells, CMS7ME and CMS17ME, and was blocked by anti-CD8 or anti-Kd mAbs. A series of peptides of human or murine c-erbB-2 compatible with the Kd binding motif was synthesized. The CTL were reactive with P1.HTR (H-2d) pulsed with three of these peptides, p63-71 (human c-erbB-2 derived), p63-71(A) (murine c-erbB-2 derived), and p780-788 (common for human and murine c-erbB-2). Spleen cells immunized in vivo and in vitro with syngeneic spleen cells pulsed with these peptides became cytotoxic for CMS17HE and/or CMS17ME, but not CMS17neo (CMS17 transduced with control vector). The growth of CMS7ME was suppressed in mice immunized with the murine c-erbB-2-derived peptide, p63-71(A) or p780-788. There was no apparent pathologic change in mice that rejected CMS7ME after vaccination with these peptides.
Insights
Peptides from the c-erbB-2 proto-oncogene can act as tumor rejection antigens. Immunization with these peptides suppressed tumor growth in mice, demonstrating their potential in cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- The proto-oncogene c-erbB-2 is expressed in various normal tissues.
- Understanding c-erbB-2's role in cancer is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate if peptides derived from c-erbB-2 function as tumor rejection antigens.
- To assess the potential of c-erbB-2 peptides in cancer immunotherapy.
Main Methods:
- Transduction of fibrosarcoma cell lines with human and murine c-erbB-2 cDNA.
- Generation and characterization of cytotoxic T lymphocytes (CTLs) against c-erbB-2-expressing cells.
- Synthesis and testing of c-erbB-2 derived peptides for CTL reactivity and tumor suppression.
Main Results:
- Immunization with c-erbB-2-transduced cells suppressed tumor growth.
- CTLs generated against c-erbB-2 recognized both human and murine c-erbB-2 expressing cells.
- Specific c-erbB-2 peptides induced CTL responses and suppressed tumor growth without apparent pathology.
Conclusions:
- Peptides derived from c-erbB-2 can function as tumor rejection antigens.
- Targeting c-erbB-2 with peptide-based vaccines shows promise for cancer immunotherapy.
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