Tanaka Motoyuki, Yamada Masaharu, Ono Toshiro, Noguchi Yuji, Uenaka Akiko, Ota Seisuke, Hata Hidenori, Harada Mine, Tanimoto Mitsune, Nakayama Eiichi
Department of Immunology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Cancer Sci. 2004 Feb;95(2):154-9. doi: 10.1111/j.1349-7006.2004.tb03197.x.
A DNA vaccine for inducing a tumor immune response was investigated using a well-characterized murine model tumor antigen. We demonstrated that in vivo electroporation augmented the induction of IFNgamma enzyme-linked immunospot (ELISPOT) and cytotoxic T lymphocyte (CTL) generation against pRL1a peptide in BALB/c spleen cells upon immunization with RLakt plasmid. Immunization without in vivo electroporation resulted in only a marginal induction of IFNgamma ELISPOT and CTL generation. Furthermore, co-injection of GM-CSF and RLakt plasmids significantly enhanced the induction of IFNgamma ELISPOT and CTL generation compared to the injection of RLakt plasmid alone. Inhibition of RL male 1 tumor growth was observed by injecting BALB/c mice with GM-CSF and RLakt plasmids using in vivo electroporation, although no effect was observed against an established tumor using the same treatment. No growth inhibition was observed without in vivo electroporation. Immunization with either RLakt plasmid alone, or GM-CSF and pCIneo control plasmids using in vivo electroporation did not inhibit RL male 1 tumor growth.
利用一种特征明确的鼠模型肿瘤抗原,对一种用于诱导肿瘤免疫反应的DNA疫苗进行了研究。我们证明,在用RLakt质粒免疫后,体内电穿孔增强了BALB/c脾细胞中针对pRL1a肽的IFNγ酶联免疫斑点(ELISPOT)诱导和细胞毒性T淋巴细胞(CTL)生成。未进行体内电穿孔的免疫仅导致IFNγ ELISPOT和CTL生成的轻微诱导。此外,与单独注射RLakt质粒相比,共注射GM-CSF和RLakt质粒显著增强了IFNγ ELISPOT和CTL生成的诱导。通过对BALB/c小鼠进行体内电穿孔注射GM-CSF和RLakt质粒,观察到RL male 1肿瘤生长受到抑制,尽管使用相同处理对已形成的肿瘤未观察到效果。未进行体内电穿孔则未观察到生长抑制。单独用RLakt质粒免疫,或使用体内电穿孔的GM-CSF和pCIneo对照质粒免疫均未抑制RL male 1肿瘤生长。