Immunotherapy of spontaneous mammary carcinoma with fusions of dendritic cells and mucin 1-positive carcinoma cells.
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.
Chen
Dongshu
D
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Xia
Jianchuan
J
Tanaka
Yasuhiro
Y
Chen
Hongsong
H
Koido
Shigeo
S
Wernet
Oliver
O
Mukherjee
Pinku
P
Gendler
Sandra J
SJ
Kufe
Donald
D
Gong
Jianlin
J
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D019496:Cancer Vaccines / Q000276:immunology*; D002459:Cell Fusion; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018396:Mucin-1 / Q000276:immunology* / Q000378:metabolism; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments