Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells

Jianlin Gong, Dongshu Chen, Masahiro Kashiwaba, Yongqing Li, Ling Chen, Hideya Takeuchi, Hui Ou, Gerald J. Rowse, Sandra J Gendler, Donald Kufe

Research output: Contribution to journalArticle

213 Citations (Scopus)

Abstract

Immunological unresponsiveness established by the elimination or anergy of self-reactive lymphocyte clones is of importance to immunization against tumor-associated antigens. In this study, we have investigated induction of immunity against the human MUC1 carcinoma-associated antigen in MUC1 transgenic mice unresponsive to MUC1 antigen. Immunization of adult MUC1 transgenic mice with irradiated MUC1-positive tumor cells was unsuccessful in reversing unresponsiveness to MUC1. By contrast, fusions of dendritic cells with MUC1-positive tumor cells induced cellular and humoral immunity against MUC1. Immunization with the dendritic cell fusions that express MUC1 resulted in the rejection of established metastases and no apparent autoimmunity against normal tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor-associated antigen is reversible by immunization with heterokaryons of dendritic cells and MUC1-positive carcinoma cells.

Original languageEnglish (US)
Pages (from-to)6279-6283
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number11
DOIs
StatePublished - May 26 1998

Fingerprint

Dendritic Cells
Transgenic Mice
Immunization
Carcinoma
Antigens
Neoplasm Antigens
Tumor-Associated Carbohydrate Antigens
Cell Fusion
Humoral Immunity
Autoimmunity
Cellular Immunity
Immunity
Neoplasms
Clone Cells
Lymphocytes
Neoplasm Metastasis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells. / Gong, Jianlin; Chen, Dongshu; Kashiwaba, Masahiro; Li, Yongqing; Chen, Ling; Takeuchi, Hideya; Ou, Hui; Rowse, Gerald J.; Gendler, Sandra J; Kufe, Donald.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 11, 26.05.1998, p. 6279-6283.

Research output: Contribution to journalArticle

Gong, Jianlin ; Chen, Dongshu ; Kashiwaba, Masahiro ; Li, Yongqing ; Chen, Ling ; Takeuchi, Hideya ; Ou, Hui ; Rowse, Gerald J. ; Gendler, Sandra J ; Kufe, Donald. / Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 11. pp. 6279-6283.
@article{8b6793f8f7234a6e93772b422e0060f2,
title = "Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells",
abstract = "Immunological unresponsiveness established by the elimination or anergy of self-reactive lymphocyte clones is of importance to immunization against tumor-associated antigens. In this study, we have investigated induction of immunity against the human MUC1 carcinoma-associated antigen in MUC1 transgenic mice unresponsive to MUC1 antigen. Immunization of adult MUC1 transgenic mice with irradiated MUC1-positive tumor cells was unsuccessful in reversing unresponsiveness to MUC1. By contrast, fusions of dendritic cells with MUC1-positive tumor cells induced cellular and humoral immunity against MUC1. Immunization with the dendritic cell fusions that express MUC1 resulted in the rejection of established metastases and no apparent autoimmunity against normal tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor-associated antigen is reversible by immunization with heterokaryons of dendritic cells and MUC1-positive carcinoma cells.",
author = "Jianlin Gong and Dongshu Chen and Masahiro Kashiwaba and Yongqing Li and Ling Chen and Hideya Takeuchi and Hui Ou and Rowse, {Gerald J.} and Gendler, {Sandra J} and Donald Kufe",
year = "1998",
month = "5",
day = "26",
doi = "10.1073/pnas.95.11.6279",
language = "English (US)",
volume = "95",
pages = "6279--6283",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "11",

}

TY - JOUR

T1 - Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells

AU - Gong, Jianlin

AU - Chen, Dongshu

AU - Kashiwaba, Masahiro

AU - Li, Yongqing

AU - Chen, Ling

AU - Takeuchi, Hideya

AU - Ou, Hui

AU - Rowse, Gerald J.

AU - Gendler, Sandra J

AU - Kufe, Donald

PY - 1998/5/26

Y1 - 1998/5/26

N2 - Immunological unresponsiveness established by the elimination or anergy of self-reactive lymphocyte clones is of importance to immunization against tumor-associated antigens. In this study, we have investigated induction of immunity against the human MUC1 carcinoma-associated antigen in MUC1 transgenic mice unresponsive to MUC1 antigen. Immunization of adult MUC1 transgenic mice with irradiated MUC1-positive tumor cells was unsuccessful in reversing unresponsiveness to MUC1. By contrast, fusions of dendritic cells with MUC1-positive tumor cells induced cellular and humoral immunity against MUC1. Immunization with the dendritic cell fusions that express MUC1 resulted in the rejection of established metastases and no apparent autoimmunity against normal tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor-associated antigen is reversible by immunization with heterokaryons of dendritic cells and MUC1-positive carcinoma cells.

AB - Immunological unresponsiveness established by the elimination or anergy of self-reactive lymphocyte clones is of importance to immunization against tumor-associated antigens. In this study, we have investigated induction of immunity against the human MUC1 carcinoma-associated antigen in MUC1 transgenic mice unresponsive to MUC1 antigen. Immunization of adult MUC1 transgenic mice with irradiated MUC1-positive tumor cells was unsuccessful in reversing unresponsiveness to MUC1. By contrast, fusions of dendritic cells with MUC1-positive tumor cells induced cellular and humoral immunity against MUC1. Immunization with the dendritic cell fusions that express MUC1 resulted in the rejection of established metastases and no apparent autoimmunity against normal tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor-associated antigen is reversible by immunization with heterokaryons of dendritic cells and MUC1-positive carcinoma cells.

UR - http://www.scopus.com/inward/record.url?scp=13144268565&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13144268565&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.11.6279

DO - 10.1073/pnas.95.11.6279

M3 - Article

C2 - 9600956

AN - SCOPUS:13144268565

VL - 95

SP - 6279

EP - 6283

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 11

ER -