Cyclophosphamide enhances the CTL precursor frequency in mice immunized with MUC1-mannan fusion protein (M-FP).
We have previously described the induction of murine CD8+ major histocompatibility complex class I restricted cytotoxic T cells to the 20 amino acid repeat region of human Mucin 1 (MUC1) variable number of tandem repeats region--a mucin greatly increased in expression in breast cancer and proposed as a target for immunotherapy. Mannan-MUC1 immunization protocol induces a high cytotoxic T lymphocyte (CTL) frequency, and some protection of mice against a tumor challenge. The CTL frequency can be substantially increased using cyclophosphamide (Cy), from 1/84,900 without Cy to 1/8,100 with Cy. Furthermore, in the presence of Cy, established tumors are rapidly eradicated, which does not happen in its absence. Cy clearly gives a major increase in the frequency of CTL precursors (CTLp) to MUC1 and could be of therapeutic value in patients.
Apostolopoulos
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V
Austin Research Institute, Heidelberg, Victoria, Australia.
Popovski
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V
McKenzie
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IF
D000818:Animals; D000912:Antibodies, Neoplasm / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods; D007167:Immunotherapy; D007958:Leukocyte Count; D008351:Mannans / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018396:Mucin-1 / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000628:therapy; D015514:Oncogene Proteins, Fusion / Q000276:immunology*; D013234:Stem Cells; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects*
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D008351:Mannans; D018396:Mucin-1; D015514:Oncogene Proteins, Fusion; D003520:Cyclophosphamide