Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice

Yasuhiro Tanaka; Shigeo Koido; Dongshu Chen; Sandra J. Gendler; Donald Kufe; Jianlin Gong

doi:10.1006/clim.2001.5112

Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice

Yasuhiro Tanaka, Shigeo Koido, Dongshu Chen, Sandra J. Gendler, Donald Kufe, Jianlin Gong

Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

Fusions of autologous tumor cells with allogeneic dendritic cells (DC) represent an approach for the induction of antitumor immunity. In the present studies, we investigated the antitumor effects of vaccinating MUC1-transgenic (MUC1.Tg) mice with MC38/MUC1 carcinoma cells fused to allogeneic DC from BALB/c mice (allo-DC, H-2^d) or syngeneic DC from C57BL/6 mice (syn-DC, H-2^b). Both allo and syn fusion cells (FC/MUC1) expressed MHC class II, costimulatory molecules, and the MUC1 antigen. Alloo-FC/MUC1 exhibited dual expression of MHC class I haplotypes (H-2^d/H-2^b) and MUC1 antigen. By contrast, only H-2^b and MUC1 antigen were expressed by syn-FC/MUC1. CTLs from MUC1.Tg mice immunized with allo- or syn-FC/MUC1 fusion cells lysed MC38/MUC1 targets. Moreover, immunization with allo- or syn-FC/MUC1 was effective in eliminating established MUC1-positive pulmonary metastases in MUC1.Tg mice. These results indicate that immunization of MUC1.Tg mice with syn- or allo-FC/MUC1 is effective in reversing immunologic unresponsiveness to MUC1 antigen and inducing immunity against MUC1-positive tumors. The findings in the present study have broader clinical implications for fusion cell vaccines.

Original language	English (US)
Pages (from-to)	192-200
Number of pages	9
Journal	Clinical Immunology
Volume	101
Issue number	2
DOIs	https://doi.org/10.1006/clim.2001.5112
State	Published - 2001

Keywords

Allogeneic and syngeneic DC fusions
Anti-tumor immunity
Fusion cell vaccines
Reversal of tolerance to MUC1

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1006/clim.2001.5112

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@article{013d31a4e8454f66b9667e840501f631,

title = "Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice",

abstract = "Fusions of autologous tumor cells with allogeneic dendritic cells (DC) represent an approach for the induction of antitumor immunity. In the present studies, we investigated the antitumor effects of vaccinating MUC1-transgenic (MUC1.Tg) mice with MC38/MUC1 carcinoma cells fused to allogeneic DC from BALB/c mice (allo-DC, H-2d) or syngeneic DC from C57BL/6 mice (syn-DC, H-2b). Both allo and syn fusion cells (FC/MUC1) expressed MHC class II, costimulatory molecules, and the MUC1 antigen. Alloo-FC/MUC1 exhibited dual expression of MHC class I haplotypes (H-2d/H-2b) and MUC1 antigen. By contrast, only H-2b and MUC1 antigen were expressed by syn-FC/MUC1. CTLs from MUC1.Tg mice immunized with allo- or syn-FC/MUC1 fusion cells lysed MC38/MUC1 targets. Moreover, immunization with allo- or syn-FC/MUC1 was effective in eliminating established MUC1-positive pulmonary metastases in MUC1.Tg mice. These results indicate that immunization of MUC1.Tg mice with syn- or allo-FC/MUC1 is effective in reversing immunologic unresponsiveness to MUC1 antigen and inducing immunity against MUC1-positive tumors. The findings in the present study have broader clinical implications for fusion cell vaccines.",

keywords = "Allogeneic and syngeneic DC fusions, Anti-tumor immunity, Fusion cell vaccines, Reversal of tolerance to MUC1",

author = "Yasuhiro Tanaka and Shigeo Koido and Dongshu Chen and Gendler, {Sandra J.} and Donald Kufe and Jianlin Gong",

note = "Funding Information: This work was supported by National Cancer Institute Grant R01 CA87057-01, Grant 990344 by the U.S. Department of Defense Breast Cancer Research programs, and Komen Breast Grant 9825 awarded by the Susan G. Komen Breast Cancer Foundation.",

year = "2001",

doi = "10.1006/clim.2001.5112",

language = "English (US)",

volume = "101",

pages = "192--200",

journal = "Clinical Immunology",

issn = "1521-6616",

publisher = "Academic Press Inc.",

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TY - JOUR

T1 - Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice

AU - Tanaka, Yasuhiro

AU - Koido, Shigeo

AU - Chen, Dongshu

AU - Gendler, Sandra J.

AU - Kufe, Donald

AU - Gong, Jianlin

N1 - Funding Information: This work was supported by National Cancer Institute Grant R01 CA87057-01, Grant 990344 by the U.S. Department of Defense Breast Cancer Research programs, and Komen Breast Grant 9825 awarded by the Susan G. Komen Breast Cancer Foundation.

PY - 2001

Y1 - 2001

N2 - Fusions of autologous tumor cells with allogeneic dendritic cells (DC) represent an approach for the induction of antitumor immunity. In the present studies, we investigated the antitumor effects of vaccinating MUC1-transgenic (MUC1.Tg) mice with MC38/MUC1 carcinoma cells fused to allogeneic DC from BALB/c mice (allo-DC, H-2d) or syngeneic DC from C57BL/6 mice (syn-DC, H-2b). Both allo and syn fusion cells (FC/MUC1) expressed MHC class II, costimulatory molecules, and the MUC1 antigen. Alloo-FC/MUC1 exhibited dual expression of MHC class I haplotypes (H-2d/H-2b) and MUC1 antigen. By contrast, only H-2b and MUC1 antigen were expressed by syn-FC/MUC1. CTLs from MUC1.Tg mice immunized with allo- or syn-FC/MUC1 fusion cells lysed MC38/MUC1 targets. Moreover, immunization with allo- or syn-FC/MUC1 was effective in eliminating established MUC1-positive pulmonary metastases in MUC1.Tg mice. These results indicate that immunization of MUC1.Tg mice with syn- or allo-FC/MUC1 is effective in reversing immunologic unresponsiveness to MUC1 antigen and inducing immunity against MUC1-positive tumors. The findings in the present study have broader clinical implications for fusion cell vaccines.

AB - Fusions of autologous tumor cells with allogeneic dendritic cells (DC) represent an approach for the induction of antitumor immunity. In the present studies, we investigated the antitumor effects of vaccinating MUC1-transgenic (MUC1.Tg) mice with MC38/MUC1 carcinoma cells fused to allogeneic DC from BALB/c mice (allo-DC, H-2d) or syngeneic DC from C57BL/6 mice (syn-DC, H-2b). Both allo and syn fusion cells (FC/MUC1) expressed MHC class II, costimulatory molecules, and the MUC1 antigen. Alloo-FC/MUC1 exhibited dual expression of MHC class I haplotypes (H-2d/H-2b) and MUC1 antigen. By contrast, only H-2b and MUC1 antigen were expressed by syn-FC/MUC1. CTLs from MUC1.Tg mice immunized with allo- or syn-FC/MUC1 fusion cells lysed MC38/MUC1 targets. Moreover, immunization with allo- or syn-FC/MUC1 was effective in eliminating established MUC1-positive pulmonary metastases in MUC1.Tg mice. These results indicate that immunization of MUC1.Tg mice with syn- or allo-FC/MUC1 is effective in reversing immunologic unresponsiveness to MUC1 antigen and inducing immunity against MUC1-positive tumors. The findings in the present study have broader clinical implications for fusion cell vaccines.

KW - Allogeneic and syngeneic DC fusions

KW - Anti-tumor immunity

KW - Fusion cell vaccines

KW - Reversal of tolerance to MUC1

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DO - 10.1006/clim.2001.5112

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AN - SCOPUS:0035181956

SN - 1521-6616

VL - 101

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EP - 200

JO - Clinical Immunology

JF - Clinical Immunology

IS - 2

ER -

Vaccination with allogeneic dendritic cells fused to carcinoma cells induces antitumor immunity in MUC1 transgenic mice

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