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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma.
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Influence of interleukin 12 on p53 peptide vaccination against established Meth A sarcoma.

机译：白介素12对已建立的Meth A肉瘤的p53肽疫苗的影响。

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摘要

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 of1 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.
机译：已知BALB / c鼠肉瘤Meth A在p53中具有三个错义点突变。我们先前曾报道，包含密码子234突变产物（称为234CM）的九聚体肽可引发234CM特异性细胞毒性T细胞，并且在肿瘤激发前用234CM佐剂免疫可抑制Meth A的生长。由于白介素12（IL-12）已显示对已建立的肿瘤具有抗肿瘤活性和免疫调节活性，因此我们分析了其对p53肽免疫和Meth A生长的影响。单独多次注射IL-12（每周4次，共2周）导致已建立的Meth A肉瘤消退，并且这种作用与剂量有关。在甲硫氨酸激发之前进行IL-12治疗几乎没有或没有抗肿瘤活性。为了评估IL-12对234CM特异性细胞毒性T淋巴细胞生成的影响，在体外用234CM敏化了经234CM免疫佐剂并注射了各种剂量的IL-12的BALB / c小鼠的脾细胞。多次注射1 ng IL-12诱导了对以234CM脉冲的靶细胞的最高细胞毒性。较高剂量的IL-12可抑制234CM特异性细胞毒性T细胞生成。在QS-21佐剂中用234CM免疫的小鼠，并用1 ng IL-12拒绝的已建立的Meth A肉瘤治疗。在1QS-21或仅用QS-21中，用1 ng IL-12进行比较处理但用234CW肽（234CM的野生型对应物）免疫的小鼠表现出进行性肿瘤生长。

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