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| Therapy of murine tumors with p53 wild-type and mutant sequence peptide-based vaccines |
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| Author(s): Mayordomo JI, Loftus DJ, Sakamoto H, DeCesare CM, Appasamy PM, Lotze MT, Storkus WJ, Appella E, DeLeo AB |
| Source: JOURNAL OF EXPERIMENTAL MEDICINE Volume: 183 Issue: 4 Pages: 1357-1365 Published: APR 1 1996 |
| Times Cited: 203 References: 41 |
| Abstract: The BALB/c Meth A sarcoma carries a p53 missense mutation at codon 234, which occurs in a peptide, termed 234CM, capable of being presented to cytotoxic T lymphocytes (CTL) by H-2K(d) molecules (Noguchi, Y., E.C. Richards, Y.-T. Chen, and L.J. Old. 1994. Proc. Natl. Acad. Sci. USA. 91:3171-3175). Immunization of BALB/c mice with bone marrow-derived dendritic cells (DC), generated in the presence of granulocyte macrophage colony-stimulating factor and interleukin 4, and prepulsed with the Meth A p53 mutant peptide, induced CTL that specifically recognized peptide-pulsed P815 cells, as well as Meth A cells naturally expressing this epitope. Immunization with this vaccine also protected naive mice from a subsequent tumor challenge, and it inhibited tumor growth in mice bearing day 7 subcutaneous Meth A tumors. We additionally determined that immunization of BALB/c mice with DC pulsed with the p53 peptide containing the wild-type residue at position 234, 234CW, induced peptide-specific CTL that reacted against several methylcholanthrene-induced BALB/c sarcomas, including CMS4 sarcoma, and rejection of CMS4 sarcoma in vaccination and therapy (day 7) protocols. These results support the efficacy of DC-based, p53-derived peptide vaccines for the immunotherapy of cancer. The translational potential of this strategy is enhanced by previous reports showing that DC can readily be generated from human peripheral blood lymphocytes. |
| Document Type: Article |
| Language: English |
Addresses:
1. UNIV PITTSBURGH, INST CANC, DIV BASIC RES, PITTSBURGH, PA 15213 USA
2. UNIV PITTSBURGH, SCH MED, DEPT MOLEC GENET & BIOCHEM, PITTSBURGH, PA 15213 USA
3. UNIV PITTSBURGH, SCH MED, DEPT PATHOL, PITTSBURGH, PA 15213 USA
4. UNIV PITTSBURGH, SCH MED, DEPT SURG, PITTSBURGH, PA 15213 USA
5. NCI, BETHESDA, MD 20892 USA |
| Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021 |
| Subject Category: Immunology; Medicine, Research & Experimental |
| IDS Number: UH144 |
| ISSN: 0022-1007 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |