PMID- 19188163 OWN - NLM STAT- MEDLINE DCOM- 20090716 LR - 20201222 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 15 IP - 3 DP - 2009 Feb 1 TI - A novel human Her-2/neu chimeric molecule expressed by Listeria monocytogenes can elicit potent HLA-A2 restricted CD8-positive T cell responses and impact the growth and spread of Her-2/neu-positive breast tumors. PG - 924-32 LID - 10.1158/1078-0432.CCR-08-2283 [doi] AB - PURPOSE: The aim of this study was to efficiently design a novel vaccine for human Her-2/neu-positive (hHer-2/neu) breast cancer using the live, attenuated bacterial vector Listeria monocytogenes. EXPERIMENTAL DESIGN: Three recombinant L. monocytogenes-based vaccines were generated that could express and secrete extracellular and intracellular fragments of the hHer-2/neu protein. In addition, we generated a fourth construct fusing selected portions of each individual fragment that contained most of the human leukocyte antigen (HLA) epitopes as a combination vaccine (L. monocytogenes-hHer-2/neu chimera). RESULTS: Each individual vaccine was able to either fully regress or slow tumor growth in a mouse model for Her-2/neu-positive tumors. All three vaccines could elicit immune responses directed toward human leukocyte antigen-A2 epitopes of hHer-2/neu. The L. monocytogenes-hHer-2/neu chimera was able to mimic responses generated by the three separate vaccines and prevent spontaneous outgrowth of tumors in an autochthonous model for Her-2/neu-positive breast cancer, induce tumor regression in transplantable models, and prevent seeding of experimental lung metastases in a murine model for metastatic breast cancer. CONCLUSION: This novel L. monocytogenes-hHer-2/neu chimera vaccine proves to be just as effective as the individual vaccines but combines the strength of all three in a single vaccination. These encouraging results support future clinical trials using this chimera vaccine and may be applicable to other cancer types expressing the Her-2/neu molecule such as colorectal and pancreatic cancer. FAU - Seavey, Matthew M AU - Seavey MM AD - Department of Microbiology, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA. FAU - Pan, Zhen-Kun AU - Pan ZK FAU - Maciag, Paulo C AU - Maciag PC FAU - Wallecha, Anu AU - Wallecha A FAU - Rivera, Sandra AU - Rivera S FAU - Paterson, Yvonne AU - Paterson Y FAU - Shahabi, Vafa AU - Shahabi V LA - eng GR - CA105008/CA/NCI NIH HHS/United States GR - R41 CA114801-01/CA/NCI NIH HHS/United States GR - T32CA09140/CA/NCI NIH HHS/United States PT - Evaluation Study PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Antigens, Neoplasm) RN - 0 (Cancer Vaccines) RN - 0 (HLA-A2 Antigen) RN - 0 (Peptide Fragments) RN - 0 (Vaccines, Synthetic) SB - IM CIN - Clin Cancer Res. 2009 Feb 1;15(3):749-51. PMID: 19188142 MH - Amino Acid Sequence MH - Animals MH - Antigens, Neoplasm/immunology MH - Breast Neoplasms/genetics/immunology/metabolism/*therapy MH - CD8-Positive T-Lymphocytes/*immunology MH - Cancer Vaccines/immunology/*therapeutic use MH - *Genes, erbB-2 MH - Genetic Vectors MH - HLA-A2 Antigen/*immunology MH - Humans MH - Listeria monocytogenes/*immunology MH - Mice MH - Molecular Sequence Data MH - Neoplasm Transplantation MH - Peptide Fragments/immunology MH - Vaccines, Synthetic/*therapeutic use EDAT- 2009/02/04 09:00 MHDA- 2009/07/17 09:00 CRDT- 2009/02/04 09:00 PHST- 2009/02/04 09:00 [entrez] PHST- 2009/02/04 09:00 [pubmed] PHST- 2009/07/17 09:00 [medline] AID - 15/3/924 [pii] AID - 10.1158/1078-0432.CCR-08-2283 [doi] PST - ppublish SO - Clin Cancer Res. 2009 Feb 1;15(3):924-32. doi: 10.1158/1078-0432.CCR-08-2283.