LEAPS Vaccine Incorporating HER-2/neu Epitope Elicits Protection That Prevents and Limits Tumor Growth and Spread of Breast Cancer in a Mouse Model.
*Cancer Vaccines/genetics/immunology/therapeutic use; Animal; Animals; Breast Neoplasms/genetics/immunology/prevention & control/therapy; CD8-Positive T-Lymphocytes/immunology; Cell Line; Cytotoxic/immunology; Disease Models; Disease Progression; Epitopes; erbB-2; Experimental/immunology/pathology/*prevention & control/*therapy; Female; Genes; Immunoglobulin G/blood; Inbred BALB C; Mammary Neoplasms; Mice; Neoplasm Metastasis/prevention & control; Proof of Concept Study; T-Lymphocyte/immunology; T-Lymphocytes; Tumor
The prototype J-LEAPS T cell vaccine for HER-2/neu breast cancer (J-HER) consists of the murine HER-2/neu66-74 H-2(d) CD8 T cell epitope covalently attached through a triglycine linker to the J-immune cell binding ligand (ICBL) (human beta2 microglobulin38-50 peptide). The J-ICBL was chosen for its potential to promote Th1/Tc1 responses. In this proof-of-concept study, the ability of J-HER to prevent or treat cancer was tested in the TUBO cell-challenged BALB/c mouse model for HER-2/neu-expressing tumors. The J-HER vaccine was administered as an emulsion in Montanide ISA-51 without the need for a more potent adjuvant. When administered as a prophylactic vaccination before tumor challenge, J-HER protected against tumor development for at least 48 days. Despite eliciting protection, antibody production in J-HER-immunized, TUBO-challenged mice was less than that in unimmunized mice. More importantly, therapeutic administration of
Rosenthal Ken S; Stone Sarah; Koski Gary; Zimmerman Daniel H
Journal of immunology research
2017
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1155/2017/3613505" target="_blank" rel="noreferrer noopener">10.1155/2017/3613505</a>
A L.E.A.P.S. heteroconjugate vaccine containing a T cell epitope from HSV-1 glycoprotein D elicits Th1 responses and protection.
Amino Acid Sequence; Animals; CD4-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/immunology; Conjugate/immunology; Delayed/immunology; Enzyme-Linked Immunosorbent Assay; Epitopes/*immunology; Female; Herpes Simplex Virus Vaccines/*immunology; Herpes Simplex/pathology/prevention & control; Herpesvirus 1; Human/*immunology; Hypersensitivity; Inbred BALB C; Interferon-gamma/biosynthesis; Lymphocyte Count; Mice; Molecular Sequence Data; Peptides/immunology; Th1 Cells/*immunology; Vaccines; Viral Envelope Proteins/*immunology
The L.E.A.P.S. heteroconjugate vaccine antigen (JgD), composed of a T cell epitope from glycoprotein D (gD(8-23)) of herpes simplex virus (HSV) linked with a peptide sequence from beta-2-microglobulin (aa38-50), elicited protection against lethal intraperitoneal (IP) challenge and prevented disease signs in most, and limited disease progression, for the rest of BALB/c mice challenged in the epidermal abrasion-zosteriform spread mouse infection model. JgD elicited a Th1 response in vaccinated mice as indicated by delayed type hypersensitivity (DTH) responses to HSV antigen, and gD and virion specific antibodies with an IgG2a/IgG1 \textgreater1. Vaccination with the JgD peptide delayed the onset of disease signs, reduced severity of the disease and reduced mortality rates in mice with different MHC backgrounds as compared to their respective control mice. CD8 cells were demonstrated as important for initiation of the immune response to JgD and CD4 cells and interferon gamma (IFN-gamma) for delivering immune protection in BALB/c mice, as indicated in monoclonal antibody ablation studies. JgD, and other
Goel N; Rong Q; Zimmerman D; Rosenthal K S
Vaccine
2003
2003-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1016/s0264-410x(03)00429-8" target="_blank" rel="noreferrer noopener">10.1016/s0264-410x(03)00429-8</a>