Lowe D B, Shearer M H, Jumper C A, Kennedy R C
Department of Microbiology and Immunology, Texas Tech University Health Sciences Center, 3601 4th Street STOP 6591, Lubbock, TX 79430-6591, USA.
Cell Mol Life Sci. 2007 Sep;64(18):2391-403. doi: 10.1007/s00018-007-7165-0.
Cancer immunotherapy faces many obstacles that include eliciting immune reactions to self antigens as well as overcoming tumor-derived immunosuppressive networks and evasion tactics. Within the vaccine arsenal for inhibiting cancer proliferation, plasmid DNA represents a novel immunization strategy that is capable of eliciting both humoral and cellular arms of the immune response in addition to being safely administered and easily engineered and manufactured. Unfortunately, while DNA vaccines have performed well in preventing and treating malignancies in animal models, their overall application in human clinical trials has not impacted cancer regression to date. Since the establishment of these early trials, progress has been made in terms of increasing DNA vaccine immunogenicity and subverting the suppressive properties of tumor cells. Therefore, the success of future plasmid DNA use in cancer patients will depend on combinatorial strategies that enhance and direct the DNA vaccine immune response while also targeting tumor evasion mechanisms.
癌症免疫疗法面临诸多障碍,包括引发针对自身抗原的免疫反应,以及克服肿瘤衍生的免疫抑制网络和逃避策略。在抑制癌症增殖的疫苗库中,质粒DNA代表了一种新型免疫策略,除了能够安全给药、易于设计和制造外,还能引发免疫反应的体液和细胞分支。不幸的是,尽管DNA疫苗在动物模型中预防和治疗恶性肿瘤方面表现良好,但迄今为止,它们在人类临床试验中的整体应用尚未对癌症消退产生影响。自这些早期试验开展以来,在提高DNA疫苗免疫原性和颠覆肿瘤细胞的抑制特性方面已取得进展。因此,未来质粒DNA在癌症患者中的成功应用将取决于组合策略,这些策略既能增强和引导DNA疫苗免疫反应,又能靶向肿瘤逃避机制。