Peptides derived from a wild-type murine proto-oncogene c-erbB-2/HER2/neu can induce CTL and tumor suppression in syngeneic hosts.
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.
Nagata
Y
Y
Second Department of Surgery, Nagasaki University School of Medicine, Japan.
Furugen
R
R
Hiasa
A
A
Ikeda
H
H
Ohta
N
N
Furukawa
K
K
Nakamura
H
H
Furukawa
K
K
Kanematsu
T
T
Shiku
H
H
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology* / Q000494:pharmacology; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D005354:Fibrosarcoma / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006131:Growth Inhibitors / Q000276:immunology; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016233:Immunotherapy, Active; D008213:Lymphocyte Activation / Q000187:drug effects; D012515:Mast-Cell Sarcoma; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology* / Q000627:therapeutic use; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D006183:H-2 Antigens; D007166:Immunosuppressive Agents; D008748:Methylcholanthrene; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; C000715470:MAS1 protein, human