Immunotherapy of spontaneous mammary carcinoma with fusions of dendritic cells and mucin 1-positive carcinoma cells
Dongshu Chen,Jianchuan Xia,Jianchuan Xia,Yasuhiro Tanaka,Hongsong Chen,Shigeo Koido,Oliver Wernet,Pinku Mukherjee,Sandra J. Gendler,Donald Kufe,Jianlin Gong,Jianlin Gong +11 more
TLDR
Results indicate that immunization with FC/MUC1 can generate an anti‐M UC1 response that is sufficient to delay the development of spontaneous mammary carcinomas and control tumour progression in MMT mice.Abstract:
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.read more
Citations
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Tolerance and immunity to MUC1 in a human MUC1 transgenic murine model
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TL;DR: The aim of this review is to analyze the activity of vaccination strategies in current clinical trials and discuss possible future directions for vaccine development and applications in the adjuvant setting.
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Strategies used for MUC1 immunotherapy: preclinical studies.
TL;DR: Evaluating the immunogenicity of MUC1 and its suitability for use in immunotherapy/vaccine for many malignancies, including solid cancers, such as breast, pancreas and ovary, and blood cancers, including multiple myeloma.
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Tumor-induced MDSC act via remote control to inhibit L-selectin-dependent adaptive immunity in lymph nodes.
Amy W. Ku,Jason B. Muhitch,Colin A. Powers,Michael Diehl,Minhyung Kim,Daniel T. Fisher,Anand P Sharda,Virginia K. Clements,Kieran L. O’Loughlin,Hans Minderman,Michelle N. Messmer,Jing Ma,Joseph J. Skitzki,Douglas A. Steeber,Bruce Walcheck,Suzanne Ostrand-Rosenberg,Scott I. Abrams,Sharon S. Evans +17 more
TL;DR: It is shown that splenic or, unexpectedly, blood-borne MDSC execute far-reaching immune suppression by reducing expression of the L-selectin lymph node (LN) homing receptor on naïve T and B cells.
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