Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma.
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.
Noguchi
Y
Y
Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Richards
E C
EC
Chen
Y T
YT
Old
L J
LJ
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D018664:Interleukin-12 / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D017354:Point Mutation; D011994:Recombinant Proteins / Q000627:therapeutic use; D012513:Sarcoma, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D014611:Vaccination
D010446:Peptide Fragments; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D018664:Interleukin-12