| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Experimental Therapeutics |
Molecular Targeting Unit [L. S., M. I. C., S. M.], Melanoma Genetic Unit [M. R.], and Immunotherapy and Gene Therapy Unit [M. P. C.], Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy; Gesellschaft für Biotechnologische Forschung (GBF) and Institute of Biochemistry, GBF-National Research Center for Biotechnology, Braunschweig, Germany [M. S.]; and Institute of Pathology, University of Milan, 20133 Milan, Italy [A. B.]
An approach to stimulating an immune response against tumors is to
transduce tumor cells with bacterial genes, which represent a "danger
signal" and can induce a wide immune response. Mycobacterium
tuberculosis genes and their encoded proteins play a pivotal
role in linking innate and cell-mediated adaptive immunity and
represent ideal candidates as immune adjuvants for tumor vaccines. The
efficacy of a cancer vaccine, obtained by transduction of a mammary
tumor cell line with the M. tuberculosis Ag38 gene, was
investigated in female mice transgenically expressing the rat
HER-2/neu proto-oncogene. These mice spontaneously
develop stochastic mammary tumors after a long latency period. The
onset of spontaneous mammary tumors was significantly delayed in mice
vaccinated with Ag38-transduced cells but not in mice
vaccinated with nontransduced cells as compared with untreated mice.
Protection from spontaneous tumor development was increased when mice
were vaccinated with the mycobacterium gene-transduced vaccine plus a
systemic administration of interleukin 12 (IL-12) at a low dose. Mice
vaccinated with nontransduced cells plus IL-12 developed tumors, with
only a slight delay in tumor appearance as compared with the control
group. Lymphocytes obtained from lymph nodes of mice vaccinated with
transduced cells secreted high levels of IFN-
.
CD3+CD8+ spleen cells derived from these mice
responded to the tumor with IFN- production. These data indicate the
efficacy of a short-term protocol of vaccinations exploiting the
adjuvant potency of a M. tuberculosis gene and low doses
of IL-12 in a model of stochastic development of mammary tumors. This
adjuvant approach may represent a promising immunotherapeutic strategy
for cancer immunization.
This article has been cited by other articles:
|
|
 |
|
  M. H. Manjili, X.-Y. Wang, X. Chen, T. Martin, E. A. Repasky, R. Henderson, and J. R. Subjeck HSP110-HER2/neu Chaperone Complex Vaccine Induces Protective Immunity Against Spontaneous Mammary Tumors in HER-2/neu Transgenic Mice J. Immunol., October 15, 2003; 171(8): 4054 - 4061. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. K. Dakappagari, J. Pyles, R. Parihar, W. E. Carson, D. C. Young, and P. T. P. Kaumaya A Chimeric Multi-Human Epidermal Growth Factor Receptor-2 B Cell Epitope Peptide Vaccine Mediates Superior Antitumor Responses J. Immunol., April 15, 2003; 170(8): 4242 - 4253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. SFONDRINI, D. BESUSSO, C. RUMIO, M. RODOLFO, S. MENARD, and A. BALSARI Prevention of spontaneous mammary adenocarcinoma in HER-2/neu transgenic mice by foreign DNA FASEB J, November 1, 2002; 16(13): 1749 - 1754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Sfondrini, D. Besusso, M. T. Zoia, M. Rodolfo, A. M. Invernizzi, M. Taniguchi, T. Nakayama, M. P. Colombo, S. Menard, and A. Balsari Absence of the CD1 Molecule Up-Regulates Antitumor Activity Induced by CpG Oligodeoxynucleotides in Mice J. Immunol., July 1, 2002; 169(1): 151 - 158. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Cell Growth & Differentiation |
