Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma Journal Article
| Authors: | Noguchi, Y.; Richards, E. C.; Chen, Y. T.; Old, L. J. |
| Article Title: | Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma |
| Abstract: | BALB/c murine sarcoma Meth A is known to have three missense point mutations in p53. We previously reported that a nonamer peptide containing the codon 234 mutational product (designated 234CM) elicited 234CM-specific cytotoxic T cells and that immunization with 234CM in adjuvant before tumor challenge inhibited Meth A growth. Because interleukin 12 (IL-12) has been shown to have antitumor activity against established tumors and immunomodulatory activities, we analyzed its effect on p53 peptide immunization and Meth A growth. Multiple injections of IL-12 alone (4 times a week for 2 weeks) caused regression of established Meth A sarcoma, and this effect was dose dependent. IL-12 treatment prior to Meth A challenge had little or no antitumor activity. To evaluate the effect of IL-12 on the generation of 234CM-specific cytotoxic T lymphocytes, spleen cells from BALB/c mice immunized with 234CM in adjuvant and injected with various doses of IL-12 were sensitized with 234CM in vitro. Multiple injections of 1 ng of IL-12 induced the highest cytotoxicity against target cells pulsed with 234CM. Higher doses of IL-12 suppressed 234CM-specific cytotoxic T-cell generation. Mice immunized with 234CM in QS-21 adjuvant and treated with 1 ng of IL-12 rejected established Meth A sarcoma. Mice comparably treated with 1 ng of IL-12 but immunized with 234CW peptide (the wild-type counterpart to 234CM) in QS-21 or with QS-21 alone showed progressive tumor growth. |
| Keywords: | nonhuman; animal cell; mouse; animal; mice; animal experiment; animal model; antineoplastic activity; cytotoxicity; protein p53; mice, inbred balb c; time factors; animalia; sarcoma; amino acid sequence; molecular sequence data; cancer vaccine; cancer vaccines; peptide fragments; recombinant proteins; vaccination; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; murinae; immunomodulation; tumor growth; codon; point mutation; interleukin 12; spleen cell; tumor immunology; sarcoma, experimental; interleukin-12; female; priority journal; article |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 92 |
| Issue: | 6 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1995-03-14 |
| Start Page: | 2219 |
| End Page: | 2223 |
| Language: | English |
| DOI: | 10.1073/pnas.92.6.2219 |
| PUBMED: | 7892250 |
| PROVIDER: | scopus |
| PMCID: | PMC42455 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
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