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- W2983288885 abstract "1278 MUC1 (mucin 1) is a transmembrane glycoprotein normally expressed on the ductal epithelia of the pancreas, breast, prostate, colon, and lung. However, in adenocarcinomas of these organs, this self-antigen is over-expressed and aberrantly glycosylated, thereby making it a promising tumor-associated antigen. Immunotherapy targeting tumor cells expressing this form of MUC1 could have great therapeutic value. Towards this end, we developed a DNA vaccine comprised of two plasmids encoding MUC1 (pMUC1) and interleukin-18 (pIL-18), and found that it protects MUC1 transgenic mice from subcutaneous tumor challenge by inducing MUC1-specific cellular immunity. We have now examined the possibility of targeting pulmonary metastases with pMUC1/pIL-18 DNA immunization in both preventive and therapeutic settings in MUC1 transgenic mice. We found that intradermal vaccination of pMUC1 DNA alone was insufficient to elicit anti-tumor effects, as measured by incidence of lung metastasis and number of tumor nodules. However, co-administration of pMUC1 with an adjuvant plasmid encoding IL-18 (pIL-18) prior to tumor challenge dramatically reduced the incidence of experimental tumor metastases in the lung. Mice immunized with pMUC1/pIL-18 also showed a prolonged survival compared to control mice. Furthermore, mice immunized with pMUC1/pIL-18 were protected from challenge with MUC1+ tumor cells, but not from MUC1- tumors, indicating that the anti-tumor effect is antigen-specific. Finally, pMUC1/pIL-18 DNA vaccination was effective in treating pre-established pulmonary metastases. Collectively, these results demonstrate that vaccination with pMUC1/pIL-18 breaks tolerance to MUC1 and induces antigen-specific immunity with protective and therapeutic benefit. This suggests that pMUC1/pIL-18 DNA vaccination may provide clinical benefit for cancer patients with MUC1+ tumors." @default.
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- W2983288885 date "2004-04-01" @default.
- W2983288885 modified "2023-09-25" @default.
- W2983288885 title "Intradermal vaccination of MUC1 transgenic mice with MUC1/IL-18 plasmid DNA inhibits experimental pulmonary metastases" @default.
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