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Immunology

Reduction of Established Spontaneous Mammary Carcinoma Metastases following Immunotherapy with Major Histocompatibility Complex Class II and B7.1 Cell-based Tumor Vaccines

Beth A. Pulaski and Suzanne Ostrand-Rosenberg
Beth A. Pulaski
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Suzanne Ostrand-Rosenberg
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DOI:  Published April 1998
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Abstract

For many cancer patients, removal of primary tumor is curative; however, if metastatic lesions exist and are not responsive to treatment, survival is limited. Although immunotherapy is actively being tested in animal models against primary tumors and experimental metastases (i.v. induced), very few studies have examined immunotherapy of spontaneous, established metastatic disease. The shortage of such studies can be attributed to the paucity of adequate animal models and to the concern that multiple metastatic lesions may be more resistant to immunotherapy than a localized primary tumor. Here, we use the BALB/c-derived mouse mammary carcinoma, 4T1, and show that this tumor very closely models human breast cancer in its immunogenicity, metastatic properties, and growth characteristics. Therapy studies demonstrate that treatment of mice with established primary and metastatic disease with MHC class II and B7.1-transfected tumor cells reduces or eliminates established spontaneous metastases but has no impact on primary tumor growth. These studies indicate that cell-based vaccines targeting the activation of CD4+ and CD8+ T cells may be effective agents for the treatment of malignancies, such as breast cancer, where the primary tumor is curable by conventional methods, but metastatic lesions remain refractile to current treatment modalities.

Footnotes

  • ↵1 This work was supported by United States Army Research and Development Command Grant DAMD17-94-J-4323, NIH Grant RO1 CA52527, and United States Army Research and Development Command Postdoctoral Fellowship DAMD17-97-1-7152 (to B. A. P.).

  • ↵2 To whom requests for reprints should be addressed, at Department of Biological Sciences, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250.

  • Received November 3, 1997.
  • Accepted January 29, 1998.
  • ©1998 American Association for Cancer Research.
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April 1998
Volume 58, Issue 7
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Reduction of Established Spontaneous Mammary Carcinoma Metastases following Immunotherapy with Major Histocompatibility Complex Class II and B7.1 Cell-based Tumor Vaccines
Beth A. Pulaski and Suzanne Ostrand-Rosenberg
Cancer Res April 1 1998 (58) (7) 1486-1493;

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Reduction of Established Spontaneous Mammary Carcinoma Metastases following Immunotherapy with Major Histocompatibility Complex Class II and B7.1 Cell-based Tumor Vaccines
Beth A. Pulaski and Suzanne Ostrand-Rosenberg
Cancer Res April 1 1998 (58) (7) 1486-1493;
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