Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine

Carla De Giovanni, Giordano Nicoletti, Lorena Landuzzi, Annalisa Astolfi, Stefania Croci, Alberto Comes, Silvano Ferrini, Raffaella Meazza, Manuela Iezzi, Emma Di Carlo, Piero Musiani, Federica Cavallo, Patrizia Nanni, Pier Luigi Lollini

Research output: Contribution to journalArticle

Abstract

This study evaluated the ability of cytokine-engineered allogeneic (H-2q) HER-2/neu-positive cells to prevent tumor development in mammary cancer-prone virgin female BALB/c (H-2d) mice transgenic for the transforming rat HER-2/neu oncogene (BALB-neuT mice). Repeated vaccinations with cells engineered to release interleukin (IL)-2, IL-12, IL-15, or IFN-γ showed that IL-12-engineered cell vaccines had the most powerful immunopreventive activity, with >80% of 1-year-old BALB-neuT mice free of tumors. On the contrary all of the untreated mice and all of the mice vaccinated with IL-12-engineered cells lacking either HER-2/neu or allogeneic antigens developed mammary carcinomas within 22 or 33 weeks, respectively. Whole mount, histology, immunohistochemistry, and gene expression profile analysis showed that vaccination with IL-12-engineered cells maintained 26-week mammary glands free of neoplastic growth, with a gene expression profile that clustered with that of untreated preneoplastic glands. The IL-12-engineered cell vaccine elicited a high production of IFN-γ and IL-4 and a strong anti-HER-2/neu antibody response. Immune protection was lost or markedly impaired in BALB-neuT mice lacking IFN-γ or antibody production, respectively. The protection afforded by the IL-12-engineered cell vaccine was equal to that provided by the systemic administration of recombinant IL-12 in combination with HER-2/neu H-2q cell vaccine. However, IL-12-engineered cell vaccine induced much lower circulating IL-12 and IFN-γ and therefore lower potential side effects and systemic toxicity.

Original languageEnglish
Pages (from-to)4001-4009
Number of pages9
JournalCancer Research
Volume64
Issue number11
DOIs
Publication statusPublished - Jun 1 2004

Fingerprint

Interleukin-12
Vaccines
Breast Neoplasms
Transcriptome
Antibody Formation
Vaccination
Transgenic Rats
Interleukin-15
Human Mammary Glands
Oncogenes
Interleukin-4
Interleukin-2
Neoplasms
Histology
Immunohistochemistry
Cytokines
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine. / De Giovanni, Carla; Nicoletti, Giordano; Landuzzi, Lorena; Astolfi, Annalisa; Croci, Stefania; Comes, Alberto; Ferrini, Silvano; Meazza, Raffaella; Iezzi, Manuela; Di Carlo, Emma; Musiani, Piero; Cavallo, Federica; Nanni, Patrizia; Lollini, Pier Luigi.

In: Cancer Research, Vol. 64, No. 11, 01.06.2004, p. 4001-4009.

Research output: Contribution to journalArticle

De Giovanni, C, Nicoletti, G, Landuzzi, L, Astolfi, A, Croci, S, Comes, A, Ferrini, S, Meazza, R, Iezzi, M, Di Carlo, E, Musiani, P, Cavallo, F, Nanni, P & Lollini, PL 2004, 'Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine', Cancer Research, vol. 64, no. 11, pp. 4001-4009. https://doi.org/10.1158/0008-5472.CAN-03-2984
De Giovanni, Carla ; Nicoletti, Giordano ; Landuzzi, Lorena ; Astolfi, Annalisa ; Croci, Stefania ; Comes, Alberto ; Ferrini, Silvano ; Meazza, Raffaella ; Iezzi, Manuela ; Di Carlo, Emma ; Musiani, Piero ; Cavallo, Federica ; Nanni, Patrizia ; Lollini, Pier Luigi. / Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine. In: Cancer Research. 2004 ; Vol. 64, No. 11. pp. 4001-4009.
@article{0d46c0a11bb446c0a1224f23962b18ae,
title = "Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine",
abstract = "This study evaluated the ability of cytokine-engineered allogeneic (H-2q) HER-2/neu-positive cells to prevent tumor development in mammary cancer-prone virgin female BALB/c (H-2d) mice transgenic for the transforming rat HER-2/neu oncogene (BALB-neuT mice). Repeated vaccinations with cells engineered to release interleukin (IL)-2, IL-12, IL-15, or IFN-γ showed that IL-12-engineered cell vaccines had the most powerful immunopreventive activity, with >80{\%} of 1-year-old BALB-neuT mice free of tumors. On the contrary all of the untreated mice and all of the mice vaccinated with IL-12-engineered cells lacking either HER-2/neu or allogeneic antigens developed mammary carcinomas within 22 or 33 weeks, respectively. Whole mount, histology, immunohistochemistry, and gene expression profile analysis showed that vaccination with IL-12-engineered cells maintained 26-week mammary glands free of neoplastic growth, with a gene expression profile that clustered with that of untreated preneoplastic glands. The IL-12-engineered cell vaccine elicited a high production of IFN-γ and IL-4 and a strong anti-HER-2/neu antibody response. Immune protection was lost or markedly impaired in BALB-neuT mice lacking IFN-γ or antibody production, respectively. The protection afforded by the IL-12-engineered cell vaccine was equal to that provided by the systemic administration of recombinant IL-12 in combination with HER-2/neu H-2q cell vaccine. However, IL-12-engineered cell vaccine induced much lower circulating IL-12 and IFN-γ and therefore lower potential side effects and systemic toxicity.",
author = "{De Giovanni}, Carla and Giordano Nicoletti and Lorena Landuzzi and Annalisa Astolfi and Stefania Croci and Alberto Comes and Silvano Ferrini and Raffaella Meazza and Manuela Iezzi and {Di Carlo}, Emma and Piero Musiani and Federica Cavallo and Patrizia Nanni and Lollini, {Pier Luigi}",
year = "2004",
month = "6",
day = "1",
doi = "10.1158/0008-5472.CAN-03-2984",
language = "English",
volume = "64",
pages = "4001--4009",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Immunoprevention of HER-2/neu transgenic mammary carcinoma through an interleukin 12-engineered allogeneic cell vaccine

AU - De Giovanni, Carla

AU - Nicoletti, Giordano

AU - Landuzzi, Lorena

AU - Astolfi, Annalisa

AU - Croci, Stefania

AU - Comes, Alberto

AU - Ferrini, Silvano

AU - Meazza, Raffaella

AU - Iezzi, Manuela

AU - Di Carlo, Emma

AU - Musiani, Piero

AU - Cavallo, Federica

AU - Nanni, Patrizia

AU - Lollini, Pier Luigi

PY - 2004/6/1

Y1 - 2004/6/1

N2 - This study evaluated the ability of cytokine-engineered allogeneic (H-2q) HER-2/neu-positive cells to prevent tumor development in mammary cancer-prone virgin female BALB/c (H-2d) mice transgenic for the transforming rat HER-2/neu oncogene (BALB-neuT mice). Repeated vaccinations with cells engineered to release interleukin (IL)-2, IL-12, IL-15, or IFN-γ showed that IL-12-engineered cell vaccines had the most powerful immunopreventive activity, with >80% of 1-year-old BALB-neuT mice free of tumors. On the contrary all of the untreated mice and all of the mice vaccinated with IL-12-engineered cells lacking either HER-2/neu or allogeneic antigens developed mammary carcinomas within 22 or 33 weeks, respectively. Whole mount, histology, immunohistochemistry, and gene expression profile analysis showed that vaccination with IL-12-engineered cells maintained 26-week mammary glands free of neoplastic growth, with a gene expression profile that clustered with that of untreated preneoplastic glands. The IL-12-engineered cell vaccine elicited a high production of IFN-γ and IL-4 and a strong anti-HER-2/neu antibody response. Immune protection was lost or markedly impaired in BALB-neuT mice lacking IFN-γ or antibody production, respectively. The protection afforded by the IL-12-engineered cell vaccine was equal to that provided by the systemic administration of recombinant IL-12 in combination with HER-2/neu H-2q cell vaccine. However, IL-12-engineered cell vaccine induced much lower circulating IL-12 and IFN-γ and therefore lower potential side effects and systemic toxicity.

AB - This study evaluated the ability of cytokine-engineered allogeneic (H-2q) HER-2/neu-positive cells to prevent tumor development in mammary cancer-prone virgin female BALB/c (H-2d) mice transgenic for the transforming rat HER-2/neu oncogene (BALB-neuT mice). Repeated vaccinations with cells engineered to release interleukin (IL)-2, IL-12, IL-15, or IFN-γ showed that IL-12-engineered cell vaccines had the most powerful immunopreventive activity, with >80% of 1-year-old BALB-neuT mice free of tumors. On the contrary all of the untreated mice and all of the mice vaccinated with IL-12-engineered cells lacking either HER-2/neu or allogeneic antigens developed mammary carcinomas within 22 or 33 weeks, respectively. Whole mount, histology, immunohistochemistry, and gene expression profile analysis showed that vaccination with IL-12-engineered cells maintained 26-week mammary glands free of neoplastic growth, with a gene expression profile that clustered with that of untreated preneoplastic glands. The IL-12-engineered cell vaccine elicited a high production of IFN-γ and IL-4 and a strong anti-HER-2/neu antibody response. Immune protection was lost or markedly impaired in BALB-neuT mice lacking IFN-γ or antibody production, respectively. The protection afforded by the IL-12-engineered cell vaccine was equal to that provided by the systemic administration of recombinant IL-12 in combination with HER-2/neu H-2q cell vaccine. However, IL-12-engineered cell vaccine induced much lower circulating IL-12 and IFN-γ and therefore lower potential side effects and systemic toxicity.

UR - http://www.scopus.com/inward/record.url?scp=2542609804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2542609804&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-03-2984

DO - 10.1158/0008-5472.CAN-03-2984

M3 - Article

C2 - 15173014

AN - SCOPUS:2542609804

VL - 64

SP - 4001

EP - 4009

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 11

ER -