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 immuno-modulatory 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Noguchi Y,Richards EC,Chen YT,Old LJdoi
10.1073/pnas.92.6.2219subject
Has Abstractpub_date
1995-03-14 00:00:00pages
2219-23issue
6eissn
0027-8424issn
1091-6490journal_volume
92pub_type
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