New target antigens for cancer immunoprevention

P. L. Lollini, G. Nicoletti, L. Landuzzi, C. De Giovanni, P. Nanni

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Prevention of cancer through the activation of the immune system has been explored in recent years in preclinical systems thanks to the availability of several new transgenic mouse models that closely mimic the natural history of human tumors. The most thoroughly investigated model of cancer immunoprevention is the mammary carcinoma of HER-2/neu transgenic mouse. In this system it has clearly been shown that the activation of immune defences in healthy individuals can effectively prevent the subsequent onset of highly aggressive mammary carcinomas. A complete prevention was obtained using a combination of three signals (the so called "triplex" vaccine) that included the specific antigen (p185, the product of HER-2/neu) and nonspecific signals like allogeneic histocompatibility antigens and interleukin 12. The analysis of protective immune responses in models of cancer immunoprevention revealed some unexpected features, in particular the central role of antibodies in immunoprevention, at variance with conventional immunotherapy which is firmly based on cytotoxic T cells. In the HER-2/neu system anti-p185 antibodies, in addition to immunological functions leading to tumor cell lysis, inhibit p185 dimerization and induce its internalization, resulting in the inhibition of mitogenic signaling. Most current tumor antigens appear to be unsuitable targets for cancer immunoprevention. An ideal antigen should have a crucial pathogenetic role in tumor growth to avoid the selection of antigen loss variants. Downregulation of major histocompatibility complex (MHC) expression during tumor progression frequently limits antigen recognition by MHC-restricted T cells. Thus an ideal antigen for cancer immunoprevention should be recognized both by T cells and by antibodies. Antibody binding to cell surface oncogenic determinants, in addition to complement- and cell-mediated tumor cell lysis, can block mitogenic signaling and induce internalization, resulting in tumor growth arrest. A search for new tumor antigens should be conducted among molecules that are directly involved in neoplastic transformation and are recognizable by the immune response also in MHC loss variants. Novel tumor antigens fulfilling both conditions will be crucial for the development of cancer immunoprevention and will provide new targets also for cancer immunotherapy.

Original languageEnglish
Pages (from-to)221-228
Number of pages8
JournalCurrent Cancer Drug Targets
Volume5
Issue number3
DOIs
Publication statusPublished - May 2005

Fingerprint

Antigens
Neoplasms
Neoplasm Antigens
Major Histocompatibility Complex
T-Lymphocytes
Immunotherapy
Transgenic Mice
Antibodies
Breast Neoplasms
Histocompatibility Antigens
Dimerization
Interleukin-12
Growth
Anti-Idiotypic Antibodies
Immune System
Down-Regulation
Vaccines

Keywords

  • γ-interferon
  • Allogeneic MHC
  • Antibodies
  • Cancer immunoprevention
  • Cancer vaccines
  • HER-2/neu
  • Interleukin 12
  • Tumor antigens

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Cancer Research

Cite this

New target antigens for cancer immunoprevention. / Lollini, P. L.; Nicoletti, G.; Landuzzi, L.; De Giovanni, C.; Nanni, P.

In: Current Cancer Drug Targets, Vol. 5, No. 3, 05.2005, p. 221-228.

Research output: Contribution to journalArticle

Lollini, P. L. ; Nicoletti, G. ; Landuzzi, L. ; De Giovanni, C. ; Nanni, P. / New target antigens for cancer immunoprevention. In: Current Cancer Drug Targets. 2005 ; Vol. 5, No. 3. pp. 221-228.
@article{75b1510a1f5c423aafd6556ad3c86ebc,
title = "New target antigens for cancer immunoprevention",
abstract = "Prevention of cancer through the activation of the immune system has been explored in recent years in preclinical systems thanks to the availability of several new transgenic mouse models that closely mimic the natural history of human tumors. The most thoroughly investigated model of cancer immunoprevention is the mammary carcinoma of HER-2/neu transgenic mouse. In this system it has clearly been shown that the activation of immune defences in healthy individuals can effectively prevent the subsequent onset of highly aggressive mammary carcinomas. A complete prevention was obtained using a combination of three signals (the so called {"}triplex{"} vaccine) that included the specific antigen (p185, the product of HER-2/neu) and nonspecific signals like allogeneic histocompatibility antigens and interleukin 12. The analysis of protective immune responses in models of cancer immunoprevention revealed some unexpected features, in particular the central role of antibodies in immunoprevention, at variance with conventional immunotherapy which is firmly based on cytotoxic T cells. In the HER-2/neu system anti-p185 antibodies, in addition to immunological functions leading to tumor cell lysis, inhibit p185 dimerization and induce its internalization, resulting in the inhibition of mitogenic signaling. Most current tumor antigens appear to be unsuitable targets for cancer immunoprevention. An ideal antigen should have a crucial pathogenetic role in tumor growth to avoid the selection of antigen loss variants. Downregulation of major histocompatibility complex (MHC) expression during tumor progression frequently limits antigen recognition by MHC-restricted T cells. Thus an ideal antigen for cancer immunoprevention should be recognized both by T cells and by antibodies. Antibody binding to cell surface oncogenic determinants, in addition to complement- and cell-mediated tumor cell lysis, can block mitogenic signaling and induce internalization, resulting in tumor growth arrest. A search for new tumor antigens should be conducted among molecules that are directly involved in neoplastic transformation and are recognizable by the immune response also in MHC loss variants. Novel tumor antigens fulfilling both conditions will be crucial for the development of cancer immunoprevention and will provide new targets also for cancer immunotherapy.",
keywords = "γ-interferon, Allogeneic MHC, Antibodies, Cancer immunoprevention, Cancer vaccines, HER-2/neu, Interleukin 12, Tumor antigens",
author = "Lollini, {P. L.} and G. Nicoletti and L. Landuzzi and {De Giovanni}, C. and P. Nanni",
year = "2005",
month = "5",
doi = "10.2174/1568009053765762",
language = "English",
volume = "5",
pages = "221--228",
journal = "Current Cancer Drug Targets",
issn = "1568-0096",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - New target antigens for cancer immunoprevention

AU - Lollini, P. L.

AU - Nicoletti, G.

AU - Landuzzi, L.

AU - De Giovanni, C.

AU - Nanni, P.

PY - 2005/5

Y1 - 2005/5

N2 - Prevention of cancer through the activation of the immune system has been explored in recent years in preclinical systems thanks to the availability of several new transgenic mouse models that closely mimic the natural history of human tumors. The most thoroughly investigated model of cancer immunoprevention is the mammary carcinoma of HER-2/neu transgenic mouse. In this system it has clearly been shown that the activation of immune defences in healthy individuals can effectively prevent the subsequent onset of highly aggressive mammary carcinomas. A complete prevention was obtained using a combination of three signals (the so called "triplex" vaccine) that included the specific antigen (p185, the product of HER-2/neu) and nonspecific signals like allogeneic histocompatibility antigens and interleukin 12. The analysis of protective immune responses in models of cancer immunoprevention revealed some unexpected features, in particular the central role of antibodies in immunoprevention, at variance with conventional immunotherapy which is firmly based on cytotoxic T cells. In the HER-2/neu system anti-p185 antibodies, in addition to immunological functions leading to tumor cell lysis, inhibit p185 dimerization and induce its internalization, resulting in the inhibition of mitogenic signaling. Most current tumor antigens appear to be unsuitable targets for cancer immunoprevention. An ideal antigen should have a crucial pathogenetic role in tumor growth to avoid the selection of antigen loss variants. Downregulation of major histocompatibility complex (MHC) expression during tumor progression frequently limits antigen recognition by MHC-restricted T cells. Thus an ideal antigen for cancer immunoprevention should be recognized both by T cells and by antibodies. Antibody binding to cell surface oncogenic determinants, in addition to complement- and cell-mediated tumor cell lysis, can block mitogenic signaling and induce internalization, resulting in tumor growth arrest. A search for new tumor antigens should be conducted among molecules that are directly involved in neoplastic transformation and are recognizable by the immune response also in MHC loss variants. Novel tumor antigens fulfilling both conditions will be crucial for the development of cancer immunoprevention and will provide new targets also for cancer immunotherapy.

AB - Prevention of cancer through the activation of the immune system has been explored in recent years in preclinical systems thanks to the availability of several new transgenic mouse models that closely mimic the natural history of human tumors. The most thoroughly investigated model of cancer immunoprevention is the mammary carcinoma of HER-2/neu transgenic mouse. In this system it has clearly been shown that the activation of immune defences in healthy individuals can effectively prevent the subsequent onset of highly aggressive mammary carcinomas. A complete prevention was obtained using a combination of three signals (the so called "triplex" vaccine) that included the specific antigen (p185, the product of HER-2/neu) and nonspecific signals like allogeneic histocompatibility antigens and interleukin 12. The analysis of protective immune responses in models of cancer immunoprevention revealed some unexpected features, in particular the central role of antibodies in immunoprevention, at variance with conventional immunotherapy which is firmly based on cytotoxic T cells. In the HER-2/neu system anti-p185 antibodies, in addition to immunological functions leading to tumor cell lysis, inhibit p185 dimerization and induce its internalization, resulting in the inhibition of mitogenic signaling. Most current tumor antigens appear to be unsuitable targets for cancer immunoprevention. An ideal antigen should have a crucial pathogenetic role in tumor growth to avoid the selection of antigen loss variants. Downregulation of major histocompatibility complex (MHC) expression during tumor progression frequently limits antigen recognition by MHC-restricted T cells. Thus an ideal antigen for cancer immunoprevention should be recognized both by T cells and by antibodies. Antibody binding to cell surface oncogenic determinants, in addition to complement- and cell-mediated tumor cell lysis, can block mitogenic signaling and induce internalization, resulting in tumor growth arrest. A search for new tumor antigens should be conducted among molecules that are directly involved in neoplastic transformation and are recognizable by the immune response also in MHC loss variants. Novel tumor antigens fulfilling both conditions will be crucial for the development of cancer immunoprevention and will provide new targets also for cancer immunotherapy.

KW - γ-interferon

KW - Allogeneic MHC

KW - Antibodies

KW - Cancer immunoprevention

KW - Cancer vaccines

KW - HER-2/neu

KW - Interleukin 12

KW - Tumor antigens

UR - http://www.scopus.com/inward/record.url?scp=18844414093&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18844414093&partnerID=8YFLogxK

U2 - 10.2174/1568009053765762

DO - 10.2174/1568009053765762

M3 - Article

C2 - 15892621

AN - SCOPUS:18844414093

VL - 5

SP - 221

EP - 228

JO - Current Cancer Drug Targets

JF - Current Cancer Drug Targets

SN - 1568-0096

IS - 3

ER -