Department of Neurosurgery, UF Brain Tumor Immunotherapy Program, University of Florida, Gainesville, Fl USA ; Department of Pathology, Duke University Medical Center, Durham, NC USA.
Division of Neurosurgery, Department of Surgery, Duke Brain Tumor Immunotherapy Program, Duke University Medical Center, Durham, NC USA.
J Immunother Cancer. 2015 Apr 21;3:13. doi: 10.1186/s40425-015-0058-0. eCollection 2015.
Tumor-specific immunotherapy holds the promise of eradicating malignant tumors with exquisite precision without additional toxicity to standard treatments. Cancer immunotherapy has conventionally relied on cell-mediated immunity while successful infectious disease vaccines have been shown to induce humoral immunity. Efficacious cancer immunotherapeutics likely require both cellular and humoral responses, and RNA based cancer vaccines are especially suited to stimulate both arms of the immune system. RNA is inherently immunogenic, inducing innate immune responses to initiate cellular and humoral adaptive immunity, but has limited utility based on its poor in vivo stability. Early work utilized 'naked' RNA vaccines, whereas more recent efforts have attempted to encapsulate RNA thereby protecting it from degradation. However, feasibility has been limited by a lack of defined and safe targeting mechanisms for the in vivo delivery of stabilized RNA. As new cancer antigens come to the forefront with novel RNA encapsulation and targeting techniques, RNA vaccines may prove to be a vital, safe and robust method to initiate patient-specific anti-tumor efficacy.
肿瘤特异性免疫疗法有望以极高的精度消除恶性肿瘤,而不会对标准治疗产生额外的毒性。癌症免疫疗法传统上依赖于细胞介导的免疫,而成功的传染病疫苗已被证明能诱导体液免疫。有效的癌症免疫疗法可能需要细胞和体液反应,而基于 RNA 的癌症疫苗特别适合刺激免疫系统的这两个分支。RNA 具有固有免疫原性,可诱导先天免疫反应以启动细胞和体液适应性免疫,但由于其体内稳定性差,其应用有限。早期工作使用了“裸露”的 RNA 疫苗,而最近的研究则试图将 RNA 包裹起来,从而防止其降解。然而,由于缺乏针对体内稳定 RNA 递送的明确和安全的靶向机制,其可行性受到限制。随着新的癌症抗原随着新型 RNA 包封和靶向技术而出现,RNA 疫苗可能被证明是一种启动患者特异性抗肿瘤疗效的重要、安全和强大的方法。