| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Vaccine Branch and
Cancer Gene Therapy Section, Metabolism Branch, Center for Cancer Research, National Cancer Institute, and
Mouse Imaging Facility, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; and
Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy
HER-2 is an oncogenic tumor-associated Ag that is overexpressed in several human tumors including breast and ovarian cancer. The efficacy and mechanism of a HER-2-expressing recombinant adenoviral vaccine to protect against tumorigenesis was examined using HER-2 transgenic (BALB-neuT) mice, which develop spontaneous breast tumors in all 10 mammary glands, and also using a transplantable mouse tumor model. Vaccination beginning at 6–8 wk of age (through 19 wk of age) prevented development of spontaneous mammary tumors even after 50 wk, whereas the animals in the control groups had tumors in all mammary glands by 25 wk. Such long-term protection after the last boost has not been achieved previously in this transgenic mouse in which the oncogene is continuously spawning tumorigenesis. Using 
2-microglobulin-knockout, IFN-
-knockout, and B cell-deficient mice, CD4+ and CD8+ cell depletion, and Ab transfer studies, we show that induction of anti-HER-2/neu Abs are both necessary and sufficient for protection, and the IgG2a isotype is most effective. In contrast, CD8+ T cells are not necessary at all, and CD4+ T cells are necessary for only 36–48 h after immunization to provide help for B cells but not as effector cells. Equal protection in immunized mice deficient in FcRI/III excluded an FcR-mediated mechanism. Anti-HER-2 serum not only inhibited growth of mammary tumor cell lines expressing HER-2 in vitro but also protected mice from tumors in vivo, suggesting a direct action of Ab on the tumor cells. Such a vaccine may provide Ab-mediated protection against HER-2-expressing breast cancers in humans.
This article has been cited by other articles:
|
|
 |
|
  J. M. Park, M. Terabe, J. C. Steel, G. Forni, Y. Sakai, J. C. Morris, and J. A. Berzofsky Therapy of Advanced Established Murine Breast Cancer with a Recombinant Adenoviral ErbB-2/neu Vaccine Cancer Res., March 15, 2008; 68(6): 1979 - 1987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Li, S. Andreansky, G. Helguera, M. Sepassi, N. Janikashvili, J. Cantrell, C. L. LaCasse, N. Larmonier, M. L. Penichet, and E. Katsanis A chaperone protein-enriched tumor cell lysate vaccine generates protective humoral immunity in a mouse breast cancer model Mol. Cancer Ther., March 1, 2008; 7(3): 721 - 729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Czerniecki, R. E. Roses, and G. K. Koski Development of Vaccines for High-Risk Ductal Carcinoma In situ of the Breast Cancer Res., July 15, 2007; 67(14): 6531 - 6534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. D. Allen, J. T. Garrett, S. V. Rawale, A. L. Jones, G. Phillips, G. Forni, J. C. Morris, R. G. Oshima, and P. T. P. Kaumaya Peptide Vaccines of the HER-2/neu Dimerization Loop Are Effective in Inhibiting Mammary Tumor Growth In Vivo J. Immunol., July 1, 2007; 179(1): 472 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Garrett, S. Rawale, S. D. Allen, G. Phillips, G. Forni, J. C. Morris, and P. T. P. Kaumaya Novel Engineered Trastuzumab Conformational Epitopes Demonstrate In Vitro and In Vivo Antitumor Properties against HER-2/neu J. Immunol., June 1, 2007; 178(11): 7120 - 7131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Czerniecki, G. K. Koski, U. Koldovsky, S. Xu, P. A. Cohen, R. Mick, H. Nisenbaum, T. Pasha, M. Xu, K. R. Fox, et al. Targeting HER-2/neu in Early Breast Cancer Development Using Dendritic Cells with Staged Interleukin-12 Burst Secretion Cancer Res., February 15, 2007; 67(4): 1842 - 1852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Rolla, C. Nicolo, S. Malinarich, M. Orsini, G. Forni, F. Cavallo, and F. Ria Distinct and Non-Overlapping T Cell Receptor Repertoires Expanded by DNA Vaccination in Wild-Type and HER-2 Transgenic BALB/c Mice J. Immunol., December 1, 2006; 177(11): 7626 - 7633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Ambrosino, M. Spadaro, M. Iezzi, C. Curcio, G. Forni, P. Musiani, W.-Z. Wei, and F. Cavallo Immunosurveillance of erbb2 carcinogenesis in transgenic mice is concealed by a dominant regulatory T-cell self-tolerance. Cancer Res., August 1, 2006; 66(15): 7734 - 7740. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Pannellini, M. Spadaro, E. Di Carlo, E. Ambrosino, M. Iezzi, A. Amici, P. L. Lollini, G. Forni, F. Cavallo, and P. Musiani Timely DNA Vaccine Combined with Systemic IL-12 Prevents Parotid Carcinomas before a Dominant-Negative p53 Makes Their Growth Independent of HER-2/neu Expression. J. Immunol., June 15, 2006; 176(12): 7695 - 7703. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
