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Immunotherapy of spontaneous mammary carcinoma with fusions of dendritic cells and mucin 1‐positive carcinoma cells
Author(s) -
Chen Dongshu,
Xia Jianchuan,
Tanaka Yasuhiro,
Chen Hongsong,
Koido Shigeo,
Wernet Oliver,
Mukherjee Pinku,
Gendler Sandra J.,
Kufe Donald,
Gong Jianlin
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01656.x
Subject(s) - muc1 , immunotherapy , immune system , cancer research , biology , immunization , cancer , antigen , mammary gland , immunology , mucin , carcinoma , breast cancer , medicine , pathology , genetics
Summary The tumour‐associated antigen mucin 1 (MUC1) is a multifunctional protein involved in protection of mucous membranes, signal transduction, and modulation of the immune system. More than 70% of cancers overexpress MUC1, making MUC1 a potential target for immunotherapy. In the present study, MUC1 transgenic mice were crossed with syngeneic strains that express the polyomavirus middle‐T oncogene (PyMT) driven by the mouse mammary tumour virus promoter long‐terminal repeat (MMTV‐LTR). The resultant breed (MMT mice) developed spontaneous MUC1‐expressing mammary carcinomas with 100% penetrance at 8–15 weeks of age. As found in human breast cancer, the mammary carcinoma in MMT mice arose in multiple stages. Immunization with fusions of dendritic cells and MUC1‐positive tumour cells (FC/MUC1) induced MUC1‐specific immune responses that blocked or delayed the development of spontaneous breast carcinomas. In contrast, there was no delay of tumour development in MMT mice immunized with irradiated MC38/MUC1 tumour cells. The efficacy of fusion cells was closely correlated with the timing of initial immunization. Immunization with FC/MUC1 initiated in MMT mice at < 1, 1–2 and 2–3 months of age rendered 33, 5 and 0% of mice free of tumour, respectively, up to 6 months. Whereas mice immunized in the later stage of tumour development succumbed to their disease, immunization resulted in control of tumour progression and prolongation of life. These results indicate that immunization with FC/MUC1 can generate an anti‐MUC1 response that is sufficient to delay the development of spontaneous mammary carcinomas and control tumour progression in MMT mice.