Cyclophosphamide Enhances the CTL Precursor Frequency in Mice Imrnunized with MUC1-Mannan Fusion Protein (M-FP)

Abstract
We have previously described the induction of murinc CD8+ major his-tocompatibility complex class I restricted cytotoxic T cells to the 20 amino acid repeat region of human Mucinl (MUC1) variable number of tandem repeats regiona mucin greatly increased in expression in breast cancer and proposed as a target for immu-notherapy. Mannan-MUCl 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.